„Galektin-3“ – Versionsunterschied

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K M.ottenbruch verschob die Seite Benutzer:Versionen/Galectin-3 nach Galektin-3, ohne dabei eine Weiterleitung anzulegen: Verschiebung auf Wunschlemma nach Import
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{{Infobox Protein
{{Infobox_gene}}
|Name =
'''Galectin-3''' is a [[protein]] that in humans is encoded by the ''LGALS3'' [[gene]].<ref name="pmid2009535">{{cite journal | vauthors = Raz A, Carmi P, Raz T, Hogan V, Mohamed A, Wolman SR | title = Molecular cloning and chromosomal mapping of a human galactoside-binding protein | journal = Cancer Research | volume = 51 | issue = 8 | pages = 2173–8 | date = April 1991 | pmid = 2009535 }}</ref><ref name="pmid8063692">{{cite journal | vauthors = Barondes SH, Cooper DN, Gitt MA, Leffler H | title = Galectins. Structure and function of a large family of animal lectins | journal = The Journal of Biological Chemistry | volume = 269 | issue = 33 | pages = 20807–10 | date = August 1994 | doi = 10.1016/S0021-9258(17)31891-4 | pmid = 8063692 | doi-access = free }}</ref> Galectin-3 is a member of the [[lectin]] family, of which 14 [[mammal]]ian [[galectin]]s have been identified.<ref name=dumic>{{cite journal | vauthors = Dumic J, Dabelic S, Flögel M | title = Galectin-3: an open-ended story | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1760 | issue = 4 | pages = 616–35 | date = April 2006 | pmid = 16478649 | doi = 10.1016/j.bbagen.2005.12.020 }}</ref><ref name = "entrez">{{cite web | title = Entrez Gene: LGALS3 lectin, galactoside-binding, soluble, 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3958}}</ref>
|Bild = Protein LGALS3 PDB 1a3k.png
|Andere Namen = LGALS3, CBP35, GAL3, GALBP, GALIG, L31, LGALS2, MAC2, lectin, galactoside binding soluble 3, galectin 3
|Symbol = LGALS3
|PDB = {{PDB2|1A3K}}, {{PDB2|1KJL}}, {{PDB2|1KJR}}, {{PDB2|2NMN}}, {{PDB2|2NMO}}, {{PDB2|2NN8}}, {{PDB2|2XG3}}, {{PDB2|3AYA}}, {{PDB2|3AYC}}, {{PDB2|3AYD}}, {{PDB2|3AYE}}, {{PDB2|3T1L}}, {{PDB2|3T1M}}, {{PDB2|3ZSJ}}, {{PDB2|3ZSK}}, {{PDB2|3ZSL}}, {{PDB2|3ZSM}}, {{PDB2|4BLI}}, {{PDB2|4BLJ}}, {{PDB2|4BM8}}, {{PDB2|4JC1}}, {{PDB2|4JCK}}, {{PDB2|4LBJ}}, {{PDB2|4LBK}}, {{PDB2|4LBL}}, {{PDB2|4LBM}}, {{PDB2|4LBN}}, {{PDB2|4LBO}}, {{PDB2|4R9A}}, {{PDB2|4R9B}}, {{PDB2|4R9C}}, {{PDB2|4R9D}}, {{PDB2|4RL7}}, {{PDB2|4XBN}}, {{PDB2|5H9R}}, {{PDB2|5H9P}}
|Groesse = 350 Aminosäuren, 35 kDa
|PubChem =
|GeneCards = LGALS3
|UniProt = P17931
|OMIM = 153619
|MGIid = 96778
| Orthologe = {{Protein Orthologe
| Spezies1 = Mensch
| Spezies2 = Hausmaus
| S1_EntrezGene = 3958
| S1_Ensembl = ENSG00000131981
| S1_RefseqmRNA = NM_002306
| S1_RefseqProtein = NP_002297
| S1_GenLoc_db = hg38
| S1_GenLoc_chr = 14
| S1_GenLoc_start = 55124110
| S1_GenLoc_end = 55145423
| S1_Uniprot = P17931
| S2_EntrezGene = 16854
| S2_Ensembl = ENSMUSG00000050335
| S2_RefseqmRNA = NM_001145953
| S2_RefseqProtein =
| S2_GenLoc_db = mm10
| S2_GenLoc_chr = 14
| S2_GenLoc_start = 47605208
| S2_GenLoc_end = 47623617
| S2_Uniprot = P16110
}}
}}


Galectin-3 is approximately 30 kDa and, like all galectins, contains a [[carbohydrate]]-recognition-binding domain (CRD) of about 130 [[amino acid]]s that enable the specific binding of β-[[galactoside]]s.<ref name=dumic/><ref name=liu>{{cite journal | vauthors = Liu FT, Patterson RJ, Wang JL | title = Intracellular functions of galectins | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1572 | issue = 2–3 | pages = 263–73 | date = September 2002 | pmid = 12223274 | doi = 10.1016/S0304-4165(02)00313-6 | author-link1 = Fu-Tong Liu }}</ref><ref name=cooper>{{cite journal | vauthors = Cooper DN | title = Galectinomics: finding themes in complexity | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1572 | issue = 2–3 | pages = 209–31 | date = September 2002 | pmid = 12223271 | doi = 10.1016/S0304-4165(02)00310-0 }}</ref><ref name=henderson>{{cite journal | vauthors = Henderson NC, Sethi T | title = The regulation of inflammation by galectin-3 | journal = Immunological Reviews | volume = 230 | issue = 1 | pages = 160–71 | date = July 2009 | pmid = 19594635 | doi = 10.1111/j.1600-065X.2009.00794.x | s2cid = 36367366 }}.</ref>


'''Galectin-3''' ist ein [[Protein]], das beim Menschen durch das ''LGALS3''-[[Gen]] kodiert wird.<ref name="pmid2009535">{{cite journal| title = Molecular cloning and chromosomal mapping of a human galactoside-binding protein | journal = Cancer Research | volume = 51 | issue = 8 | pages = 2173–8 | date = April 1991 | pmid = 2009535 }}</ref><ref name="pmid8063692">{{cite journal | title = Galectins. Structure and function of a large family of animal lectins | journal = The Journal of Biological Chemistry | volume = 269 | issue = 33 | pages = 20807–10 | date = August 1994 | pmid = 8063692}}</ref> Galectin-3 ist ein Mitglied der [[Lektin]]-Familie, von der 14 [[Galektin]]e in Säugetieren identifiziert wurden.<ref name="dumic">{{cite journal | title = Galectin-3: an open-ended story | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1760 | issue = 4 | pages = 616–35 | date = April 2006}}</ref><ref name="entrez">{{cite web | pmid = 16478649 | title = Entrez Gene: LGALS3 lectin, galactoside-binding, soluble, 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3958}}</ref>
Galectin-3 (Gal-3) is also a member of the beta-galactoside-binding protein family that plays an important role in [[cell-cell adhesion]], [[extracellular matrix|cell-matrix]] interactions, [[macrophage]] activation, [[angiogenesis]], [[metastasis]], [[apoptosis]].


Galectin-3 ist ein Mitglied der beta-Galactosid-bindenden Proteinfamilie, die eine wichtige Rolle bei der Zell-[[Adhäsion]], extrazellulären Matrix-Wechselwirkung, [[Makrophagen]]-Aktivierung, [[Angiogenese]], bei [[Metastase]]n und der [[Apoptose]] spielt.
Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22.<ref name=dumic/><ref>{{cite journal | vauthors = Raimond J, Zimonjic DB, Mignon C, Mattei M, Popescu NC, Monsigny M, Legrand A | title = Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22 | journal = Mammalian Genome | volume = 8 | issue = 9 | pages = 706–7 | date = September 1997 | pmid = 9271684 | doi = 10.1007/s003359900548 | s2cid = 1955109 }}</ref> Galectin-3 is expressed in the [[Nucleus (cell)|nucleus]], [[cytoplasm]], [[mitochondrion]], cell surface, and [[extracellular space]].<ref name=dumic/><ref name=liu/><ref name=cooper/>


Galectin-3 wird von einem einzelnen Gen, LGALS3, codiert, das sich auf Chromosom 14, Locus q21–q22, befindet.<ref name="dumic" /><ref>{{cite journal | title = Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22 | journal = Mammalian Genome | volume = 8 | issue = 9 | pages = 706–7 | date = September 1997 | pmid = 9271684 | doi = 10.1007/s003359900548}}</ref> Galectin-3 wird im [[Zellkern]], [[Zytoplasma]], [[Mitochondrium]], der Zelloberfläche und im [[Extrazellularraum|extrazellulären Raum]] exprimiert.
== Function ==


Galectin-3 hat eine Affinität zu Beta-[[Galactoside]]n und weist eine antimikrobielle Aktivität gegen Bakterien und Pilze auf.
Galectin-3 has an affinity for [[beta-galactoside]]s and exhibits [[antimicrobial]] activity against bacteria and fungi.<ref name = "entrez"/>
Es wurde gezeigt, dass dieses [[Protein]] an den folgenden biologischen Prozessen beteiligt ist: [[Zelladhäsion]], Zellaktivierung, [[Zellwachstum]] und [[Differenzierung (Biologie)|Differenzierung]], [[Zellzyklus]] und [[Apoptose]]. Angesichts der breiten biologischen Funktionalität von Galectin-3 wurde gezeigt, dass es an [[Krebs]], [[Entzündung]], [[Fibrose]], [[Herzkrankheit]] und [[Schlaganfall]] beteiligt ist.<ref name="Sharma_2004">{{cite journal | title = Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction | journal = Circulation | volume = 110 | issue = 19 | pages = 3121–8 | date = November 2004 | pmid = 15520318 | doi = 10.1161/01.CIR.0000147181.65298.4D}}</ref><ref>{{cite journal | title = Galectin-3 mediates post-ischemic tissue remodeling | journal = Brain Research | volume = 1288 | pages = 116–24 | date = September 2009 | pmid = 19573520}}</ref> Studien haben auch gezeigt, dass die Expression von Galectin-3 an einer Vielzahl von Prozessen beteiligt ist, die mit Herzinsuffizienz verbunden sind, einschließlich Myofibroblasten-Proliferation, Fibrogenese, Gewebereparatur, Entzündung und [[Kardiales Remodeling]]..<ref name="Sharma_2004" /><ref>{{cite journal | title = N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 296 | issue = 2 | pages = H404-12 | date = February 2009 | pmid = 19098114 | pmc = 2643891 | doi = 10.1152/ajpheart.00747.2008 }}</ref><ref>{{cite journal | title = The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 409 | issue = 1–2 | pages = 96–9 | date = November 2009 | pmid = 19747906 | doi = 10.1016/j.cca.2009.09.001 }}</ref>


Galectin-3 assoziiert mit den [[Zilie|Primären Zilien]] und moduliert das Nierenzystenwachstum bei [[Zystenniere|angeborener polyzystischer Nierenerkrankung]].<ref name="pmid17148658">{{cite journal | title = Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease | journal = The American Journal of Pathology | volume = 169 | issue = 6 | pages = 1925–38 | date = December 2006 | pmid = 17148658 | pmc = 1762475 | doi = 10.2353/ajpath.2006.060245 }}</ref>
This [[protein]] has been shown to be involved in the following [[biological process]]es: [[cell adhesion]], cell activation and [[Chemoattractant|chemoattraction]], [[cell growth]] and [[Differentiation (cellular)|differentiation]], [[cell cycle]], and [[apoptosis]].<ref name=dumic/> Given galectin-3's broad biological functionality, it has been demonstrated to be involved in [[cancer]], [[inflammation]] and [[fibrosis]], [[heart disease]], and [[stroke]].<ref name=dumic/><ref name=henderson/><ref name="Sharma_2004">{{cite journal | vauthors = Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, André S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM | display-authors = 6 | title = Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction | journal = Circulation | volume = 110 | issue = 19 | pages = 3121–8 | date = November 2004 | pmid = 15520318 | doi = 10.1161/01.CIR.0000147181.65298.4D | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yan YP, Lang BT, Vemuganti R, Dempsey RJ | title = Galectin-3 mediates post-ischemic tissue remodeling | journal = Brain Research | volume = 1288 | pages = 116–24 | date = September 2009 | pmid = 19573520 | doi = 10.1016/j.brainres.2009.06.073 | s2cid = 8348013 }}</ref> Studies have also shown that the expression of galectin-3 is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and [[ventricular remodeling]].<ref name="Sharma_2004"/><ref>{{cite journal | vauthors = Liu YH, D'Ambrosio M, Liao TD, Peng H, Rhaleb NE, Sharma U, André S, Gabius HJ, Carretero OA | display-authors = 6 | title = N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 296 | issue = 2 | pages = H404-12 | date = February 2009 | pmid = 19098114 | pmc = 2643891 | doi = 10.1152/ajpheart.00747.2008 }}</ref><ref>{{cite journal | vauthors = Lin YH, Lin LY, Wu YW, Chien KL, Lee CM, Hsu RB, Chao CL, Wang SS, Hsein YC, Liao LC, Ho YL, Chen MF | display-authors = 6 | title = The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 409 | issue = 1–2 | pages = 96–9 | date = November 2009 | pmid = 19747906 | doi = 10.1016/j.cca.2009.09.001 }}</ref>


Die funktionelle Rolle von Galektinen bei der zellulären Reaktion auf Membranschäden wird immer deutlicher. Kürzlich wurde gezeigt, dass Galectin-3 [[ESCRT]]s zu beschädigten Lysosomen rekrutiert, damit diese repariert werden können.<ref>{{cite journal | title = Galectins Control mTOR in Response to Endomembrane Damage | journal = Molecular Cell | volume = 70 | issue = 1 | pages = 120–135.e8 | date = April 2018 | pmid = 29625033 | pmc = 5911935 | doi = 10.1016/j.molcel.2018.03.009 }}</ref><ref>{{cite journal | title = Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal | journal = Developmental Cell | volume = 52 | issue = 1 | pages = 69–87.e8 | date = January 2020 | pmid = 31813797 | doi = 10.1016/j.devcel.2019.10.025 | pmc = 6997950 }}</ref><ref>{{cite journal | title = AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System | journal = Molecular Cell | pages = 951–969.e9 | date = January 2020 | volume = 77 | issue = 5 | pmid = 31995728 | doi = 10.1016/j.molcel.2019.12.028 | pmc = 7785494 }}</ref>
Galectin-3 associates with the [[primary cilium]] and modulates [[renal cyst]] growth in [[congenital polycystic kidney disease]].<ref name="pmid17148658">{{cite journal | vauthors = Chiu MG, Johnson TM, Woolf AS, Dahm-Vicker EM, Long DA, Guay-Woodford L, Hillman KA, Bawumia S, Venner K, Hughes RC, Poirier F, Winyard PJ | display-authors = 6 | title = Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease | journal = The American Journal of Pathology | volume = 169 | issue = 6 | pages = 1925–38 | date = December 2006 | pmid = 17148658 | pmc = 1762475 | doi = 10.2353/ajpath.2006.060245 }}</ref>


== Einzelnachweise ==
The functional roles of [[galectin]]s in cellular response to membrane damage are rapidly expanding.<ref>{{cite journal | vauthors = Jia J, Abudu YP, Claude-Taupin A, Gu Y, Kumar S, Choi SW, Peters R, Mudd MH, Allers L, Salemi M, Phinney B, Johansen T, Deretic V | display-authors = 6 | title = Galectins Control mTOR in Response to Endomembrane Damage | journal = Molecular Cell | volume = 70 | issue = 1 | pages = 120–135.e8 | date = April 2018 | pmid = 29625033 | pmc = 5911935 | doi = 10.1016/j.molcel.2018.03.009 }}</ref><ref name="Jia_2020">{{cite journal | vauthors = Jia J, Claude-Taupin A, Gu Y, Choi SW, Peters R, Bissa B, Mudd MH, Allers L, Pallikkuth S, Lidke KA, Salemi M, Phinney B, Mari M, Reggiori F, Deretic V | display-authors = 6 | title = Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal | journal = Developmental Cell | volume = 52 | issue = 1 | pages = 69–87.e8 | date = January 2020 | pmid = 31813797 | doi = 10.1016/j.devcel.2019.10.025 | pmc = 6997950 }}</ref><ref>{{cite journal | vauthors = Jia J, Bissa B, Brecht L, Allers L, Choi SW, Gu Y, Zbinden M, Burge MR, Timmins G, Hallows K, Behrends C, Deretic V | display-authors = 6 | title = AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System | journal = Molecular Cell | pages = 951–969.e9 | date = January 2020 | volume = 77 | issue = 5 | pmid = 31995728 | doi = 10.1016/j.molcel.2019.12.028 | pmc = 7785494 }}</ref> It has recently shown that Galectin-3 recruits [[ESCRT]]s to damaged lysosomes so that lysosomes can be repaired.<ref name="Jia_2020" />
<references />


[[Kategorie:Protein]]
== Clinical significance ==
[[Kategorie:Lektin]]

[[Kategorie:Codiert auf Chromosom 14 (Mensch)]]
=== Fibrosis ===

A correlation between galectin-3 expression levels and various types of [[fibrosis]] has been found. Galectin-3 is [[Downregulation and upregulation|upregulated]] in cases of liver fibrosis, renal fibrosis, and [[idiopathic pulmonary fibrosis]] (IPF). In several studies with mice deficient in or lacking galectin-3, conditions that caused control mice to develop [[Idiopathic pulmonary fibrosis|IPF]], renal, or liver fibrosis either induced limited fibrosis or failed to induce fibrosis entirely.<ref>{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T | display-authors = 6 | title = Galectin-3 regulates myofibroblast activation and hepatic fibrosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 13 | pages = 5060–5 | date = March 2006 | pmid = 16549783 | pmc = 1458794 | doi = 10.1073/pnas.0511167103 | bibcode = 2006PNAS..103.5060H | doi-access = free }}</ref><ref>{{cite journal | vauthors = Henderson NC, Mackinnon AC, Farnworth SL, Kipari T, Haslett C, Iredale JP, Liu FT, Hughes J, Sethi T | display-authors = 6 | title = Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis | journal = The American Journal of Pathology | volume = 172 | issue = 2 | pages = 288–98 | date = February 2008 | pmid = 18202187 | pmc = 2312353 | doi = 10.2353/ajpath.2008.070726 }}</ref><ref name=IPF>{{cite journal | vauthors = Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, Simpson AJ, Forbes SJ, Hirani N, Gauldie J, Sethi T | display-authors = 6 | title = Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3 | journal = American Journal of Respiratory and Critical Care Medicine | volume = 185 | issue = 5 | pages = 537–46 | date = March 2012 | pmid = 22095546 | pmc = 3410728 | doi = 10.1164/rccm.201106-0965OC }}</ref> Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitor, TD139 and GR-MD-02 have the potential to treat fibrosis.<ref name="IPF" />

=== Cardiovascular disease ===

Elevated levels of galectin-3 have been found to be significantly associated with higher risk of death in both acute decompensated heart failure and chronic heart failure populations.<ref>{{cite journal | vauthors = van Kimmenade RR, Januzzi JL, Ellinor PT, Sharma UC, Bakker JA, Low AF, Martinez A, Crijns HJ, MacRae CA, Menheere PP, Pinto YM | display-authors = 6 | title = Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure | journal = Journal of the American College of Cardiology | volume = 48 | issue = 6 | pages = 1217–24 | date = September 2006 | pmid = 16979009 | doi = 10.1016/j.jacc.2006.03.061 | doi-access = free }}</ref><ref name="pmid20130888">{{cite journal | vauthors = Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, Van Wijngaarden J, Hillege HL, van Veldhuisen DJ | title = Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study | journal = Clinical Research in Cardiology | volume = 99 | issue = 5 | pages = 323–8 | date = May 2010 | pmid = 20130888 | pmc = 2858799 | doi = 10.1007/s00392-010-0125-y }}</ref> In normal human, [[murine]], and rat cells galectin-3 levels are low. However, as heart disease progresses, significant [[upregulation]] of galectin-3 occurs in the [[myocardium]].<ref>{{cite journal | vauthors = de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ | title = Galectin-3: a novel mediator of heart failure development and progression | journal = European Journal of Heart Failure | volume = 11 | issue = 9 | pages = 811–7 | date = September 2009 | pmid = 19648160 | doi = 10.1093/eurjhf/hfp097 | s2cid = 32686826 }}</ref>

Galectin-3 also may be used as a [[biomarker]] to identify at risk individuals, and predict patient response to different drugs and therapies. For instance, galectin-3 levels could be used in early detection of failure-prone hearts and lead to intervention strategies including broad spectrum anti-inflammatory agents.<ref name="Sharma_2004"/> One study concluded that individuals with [[Systole (medicine)|systolic]] heart failure of [[ischaemic]] origin and elevated galectin-3 levels may benefit from [[statin]] treatment.<ref>{{cite journal | vauthors = Gullestad L, Ueland T, Kjekshus J, Nymo SH, Hulthe J, Muntendam P, Adourian A, Böhm M, van Veldhuisen DJ, Komajda M, Cleland JG, Wikstrand J, McMurray JJ, Aukrust P | display-authors = 6 | title = Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) | journal = European Heart Journal | volume = 33 | issue = 18 | pages = 2290–6 | date = September 2012 | pmid = 22513778 | doi = 10.1093/eurheartj/ehs077 | doi-access = free }}</ref> Galectin-3 has also been associated as a factor promoting [[ventricular remodeling]] following [[mitral valve repair]], and may identify patients requiring additional therapies to obtain beneficial [[reverse remodeling]].<ref>{{cite journal | vauthors = Kortekaas KA, Hoogslag GE, de Boer RA, Dokter MM, Versteegh MI, Braun J, Marsan NA, Verwey HF, Delgado V, Schalij MJ, Klautz RJ | display-authors = 6 | title = Galectin-3 and left ventricular reverse remodelling after surgical mitral valve repair | journal = European Journal of Heart Failure | volume = 15 | issue = 9 | pages = 1011–8 | date = September 2013 | pmid = 23576289 | doi = 10.1093/eurjhf/hft056 | s2cid = 1252812 | doi-access = free }}</ref>

=== Cancer ===

The wide variety of effects of galectin-3 on [[cancer cell|cancerous cells]] are due to the unique structure and various interaction properties of the molecule. [[Overexpression]] and changes in the [[Protein#Cellular localization|localization]] of galectin-3 molecules affects the prognosis of the patient and targeting the actions of galectin-3 poses a promising therapeutic strategy for the development of effective [[therapeutic agent]]s for cancer treatment.

[[Overexpression]] and changes in [[Subcellular localization|sub-]] and [[wiktionary:intercellular|inter-cellular]] localization of galectin-3 are commonly seen in [[cancer]]ous conditions. The many interaction and binding properties of galectin-3 influence various cell activities based on its location. Altered galectin-3 expression can affect cancer [[cell growth]] and [[differentiation (cellular)|differentiation]], [[Chemoattractant|chemoattraction]], [[apoptosis]], [[immunosuppression]], [[angiogenesis]], [[cell adhesion|adhesion]], invasion and [[metastasis]].<ref name=Jack-of-all-trades>{{cite journal | vauthors = Newlaczyl AU, Yu LG | title = Galectin-3--a jack-of-all-trades in cancer | journal = Cancer Letters | volume = 313 | issue = 2 | pages = 123–8 | date = December 2011 | pmid = 21974805 | doi = 10.1016/j.canlet.2011.09.003 }}</ref>

Galectin-3 [[overexpression]] promotes [[neoplastic]] transformation and the maintenance of transformed [[phenotypes]] as well as enhances the [[tumour]] cell's adhesion to the [[extracellular matrix]] and increase [[metastasis|metastatic]] spreading. Galectin-3 can be either an inhibitory or a promoting [[apoptosis|apoptotic]] depending on its [[subcellular localization|sub-cellular localization]]. In immune regulation, galectin-3 can regulate immune cell activities and helps contribute to the [[tumour]] cell's evasion of the [[immune system]]. Galectin-3 also helps promote [[angiogenesis]].<ref name=Jack-of-all-trades />

The roles of galectins and galectin-3, in particular, in cancer have been heavily investigated.<ref name=Liu>{{cite journal | vauthors = Liu FT, Rabinovich GA | title = Galectins as modulators of tumour progression | journal = Nature Reviews. Cancer | volume = 5 | issue = 1 | pages = 29–41 | date = January 2005 | pmid = 15630413 | doi = 10.1038/nrc1527 | s2cid = 4849835 }}</ref> Of note, galectin-3 has been suggested to play important roles in cancer metastasis.<ref name=Reticker-Flynn>{{cite journal | vauthors = Reticker-Flynn NE, Malta DF, Winslow MM, Lamar JM, Xu MJ, Underhill GH, Hynes RO, Jacks TE, Bhatia SN | display-authors = 6 | title = A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis | journal = Nature Communications | volume = 3 | issue = 3 | pages = 1122 | year = 2012 | pmid = 23047680 | pmc = 3794716 | doi = 10.1038/ncomms2128 | bibcode = 2012NatCo...3.1122R }}</ref>

== Clinical applications ==

=== Cardiovascular risk indicator ===
[[Chronic heart failure]] has been found to be indicated by a galectin-3 tests, using the ARCHITECT [[immunochemistry]] platform developed by BG Medicine and marketed by Abbott, helping to determine which patients are most at risk for the disease. This test is also offered on the VIDAS platform marketed by bioMérieux.<ref>{{cite web|last=Ross|first=D|title=Abbott's Galectin-3 Test Provides Doctors in Europe with New Tool for Assessing the Prognosis of Chronic Heart Failure Patient|url=http://www.abbott.com/press-release/abbotts-galectin3-test-provides-doctors-in-europe-with-new-tool-for-assessing-the-prognosis-of-chr.htm|access-date=28 November 2013}}</ref> Pecta-Sol C binds to galectin-3 binding sites on the surfaces of cells as a preventative measure created by Isaac Eliaz in conjunction with EcoNugenics.<ref>{{cite journal|last=Brechka|first=Nicole | name-list-style = vanc |title=Putting the Squeeze on Cancer|year=2009|url=http://www.betternutrition.com/citrus-pectin-cancer-fighter/columns/favoritethings/1086|access-date=28 November 2013}}</ref>

Galectin-3 is [[Downregulation and upregulation|upregulated]] in patients with [[idiopathic pulmonary fibrosis]]. The cells that receive galectin-3 stimulation ([[fibroblasts]], [[epithelial cells]], and [[myofibroblasts]]) [[Downregulation and upregulation|upregulated]] the formation of [[fibrosis]] and [[collagen| collagen formation]].<ref name = "yu" >{{cite journal | vauthors = Yu L, Ruifrok WP, Meissner M, Bos EM, van Goor H, Sanjabi B, van der Harst P, Pitt B, Goldstein IJ, Koerts JA, van Veldhuisen DJ, Bank RA, van Gilst WH, Silljé HH, de Boer RA | display-authors = 6 | title = Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis | journal = Circulation: Heart Failure | volume = 6 | issue = 1 | pages = 107–17 | date = January 2013 | pmid = 23230309 | doi = 10.1161/circheartfailure.112.971168 | doi-access = free }}</ref> Fibrosis is necessary in many aspects of intrabody [[Regeneration (biology)|regeneration]]. The myocardial lining constantly undergoes necessary fibrosis, and the inhibition of galectin-3 interferes with myocardial [[fibrogenesis]]. A study concluded that pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development.<ref name = "yu" />

=== Drug development ===

[[Galecto Biotech]] in Sweden is focused on developing drugs targeting galectin-3 to treat [[fibrosis]], specifically [[idiopathic pulmonary fibrosis]].<ref>{{cite journal | vauthors = Garber K | title = Galecto Biotech | journal = Nature Biotechnology | volume = 31 | issue = 6 | pages = 481 | date = June 2013 | pmid = 23752421 | doi = 10.1038/nbt0613-481 | s2cid = 205268879 }}</ref> Galectin Therapeutics in the United States is also targeting [[galectin]]s for clinical applications. Preclinical studies demonstrate that inhibition of galectin-3 significantly reduces [[portal hypertension]] and [[fibrosis]].<ref>{{cite web|title=Galectin Therapeutics' Preclinical Data Published in PLOS ONE Show Its Galectin Inhibitors Reverse Cirrhosis and Significantly Reduce Fibrosis and Portal Hypertension|url=http://phx.corporate-ir.net/phoenix.zhtml?c=135403&p=irol-newsArticle&ID=1863329&highlight=|publisher=Globe Newswire|access-date=28 November 2013}}</ref> Galectin Therapeutics galectin-3 inhibitor GR-MD-02 (belapectin) is currently in human clinical trials for [[nonalcoholic steatohepatitis]] (NASH) and for increasing the effectiveness and reducing side effects of cancer immunotherapy.<ref>{{cite journal | vauthors = Neuschwander-Tetri BA | title = Therapeutic Landscape for NAFLD in 2020 | journal = Gastroenterology | volume = 158 | issue = 7 | pages = 1984–1998.e3 | date = May 2020 | pmid = 32061596 | doi = 10.1053/j.gastro.2020.01.051 | s2cid = 211133881 }}</ref><ref>{{cite journal | vauthors = Narayan V, Thompson EW, Demissei B, Ho JE, Januzzi JL, Ky B | title = Mechanistic Biomarkers Informative of Both Cancer and Cardiovascular Disease: JACC State-of-the-Art Review | journal = Journal of the American College of Cardiology | volume = 75 | issue = 21 | pages = 2726–2737 | date = June 2020 | pmid = 32466889 | doi = 10.1016/j.jacc.2020.03.067 | pmc = 7261288 }}</ref><ref>{{cite journal | vauthors = Martínez-Bosch N, Rodriguez-Vida A, Juanpere N, Lloreta J, Rovira A, Albanell J, Bellmunt J, Navarro P | display-authors = 6 | title = Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities | journal = Nature Reviews. Urology | volume = 16 | issue = 7 | pages = 433–445 | date = July 2019 | pmid = 31015643 | doi = 10.1038/s41585-019-0183-5 | hdl = 10261/201560 | s2cid = 128360958 | hdl-access = free }}</ref>

=== Biomarkers ===

Galectin-3 is increasingly being used as a [[biomarker|diagnostic marker]] for different cancers. It can be screened for and used as a prognostic factor to predict the progression of the cancer. Galectin-3 has varying effects in different types of cancer.<ref name="Galectin-3 biomarkers">{{cite journal | vauthors = Idikio HA | title = Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT-PCR, and logistic regression model to identify cancer cell biomarkers | journal = PLOS ONE | volume = 6 | issue = 10 | pages = e26150 | date = 19 October 2011 | pmid = 22039439 | pmc = 3198435 | doi = 10.1371/journal.pone.0026150 | url = http://pubmed.cn/22039439 | bibcode = 2011PLoSO...626150I | doi-access = free }}</ref> One approach to cancers with high galectin-3 expression is to inhibit galectin-3 to enhance treatment response.<ref>{{cite journal | vauthors = Cay T | title = Immunhistochemical expression of galectin-3 in cancer: a review of the literature | journal = Turk Patoloji Dergisi | volume = 28 | issue = 1 | pages = 1–10 | date = March 2011 | pmid = 22207425 | doi = 10.5146/tjpath.2012.01090 | series = 1 | doi-access = free }}</ref>

== Interactions ==

LGALS3 has been shown to [[Protein-protein interaction|interact]] with [[LGALS3BP]].<ref name = pmid1917996>{{cite journal | vauthors = Rosenberg I, Cherayil BJ, Isselbacher KJ, Pillai S | title = Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin | journal = The Journal of Biological Chemistry | volume = 266 | issue = 28 | pages = 18731–6 | date = October 1991 | doi = 10.1016/S0021-9258(18)55124-3 | pmid = 1917996 | doi-access = free }}</ref><ref name = pmid8390986>{{cite journal | vauthors = Koths K, Taylor E, Halenbeck R, Casipit C, Wang A | title = Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain | journal = The Journal of Biological Chemistry | volume = 268 | issue = 19 | pages = 14245–9 | date = July 1993 | doi = 10.1016/S0021-9258(19)85233-X | pmid = 8390986 | doi-access = free }}</ref><ref name = pmid11146440>{{cite journal | vauthors = Tinari N, Kuwabara I, Huflejt ME, Shen PF, Iacobelli S, Liu FT | title = Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation | journal = International Journal of Cancer | volume = 91 | issue = 2 | pages = 167–72 | date = January 2001 | pmid = 11146440 | doi = 10.1002/1097-0215(200002)9999:9999<::aid-ijc1022>3.3.co;2-q }}</ref>

In melanocytic cells LGALS3 gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | display-authors = 6 | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–76 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | s2cid = 24698373 | doi-access = free }}</ref>

== References==
{{reflist|33em}}

{{PDB Gallery|geneid=3958}}
{{NLM content}}

[[Category:Lectins]]

Version vom 31. August 2022, 09:28 Uhr

Galektin-3
Galektin-3
Andere Namen

LGALS3, CBP35, GAL3, GALBP, GALIG, L31, LGALS2, MAC2, lectin, galactoside binding soluble 3, galectin 3

Vorhandene Strukturdaten: 1A3K, 1KJL, 1KJR, 2NMN, 2NMO, 2NN8, 2XG3, 3AYA, 3AYC, 3AYD, 3AYE, 3T1L, 3T1M, 3ZSJ, 3ZSK, 3ZSL, 3ZSM, 4BLI, 4BLJ, 4BM8, 4JC1, 4JCK, 4LBJ, 4LBK, 4LBL, 4LBM, 4LBN, 4LBO, 4R9A, 4R9B, 4R9C, 4R9D, 4RL7, 4XBN, 5H9R, 5H9P

Masse/Länge Primärstruktur 350 Aminosäuren, 35 kDa
Bezeichner
Gen-Name(n) LGALS3
Externe IDs
Vorkommen
Homologie-Familie Hovergen
Orthologe
Mensch Hausmaus
Entrez 3958 16854
Ensembl ENSG00000131981 ENSMUSG00000050335
UniProt P17931 P16110
Refseq (mRNA) NM_002306 NM_001145953
Refseq (Protein) NP_002297
Genlocus Chr 14: 55.12 – 55.15 Mb Chr 14: 47.61 – 47.62 Mb
PubMed-Suche 3958 16854


Galectin-3 ist ein Protein, das beim Menschen durch das LGALS3-Gen kodiert wird.[1][2] Galectin-3 ist ein Mitglied der Lektin-Familie, von der 14 Galektine in Säugetieren identifiziert wurden.[3][4]

Galectin-3 ist ein Mitglied der beta-Galactosid-bindenden Proteinfamilie, die eine wichtige Rolle bei der Zell-Adhäsion, extrazellulären Matrix-Wechselwirkung, Makrophagen-Aktivierung, Angiogenese, bei Metastasen und der Apoptose spielt.

Galectin-3 wird von einem einzelnen Gen, LGALS3, codiert, das sich auf Chromosom 14, Locus q21–q22, befindet.[3][5] Galectin-3 wird im Zellkern, Zytoplasma, Mitochondrium, der Zelloberfläche und im extrazellulären Raum exprimiert.

Galectin-3 hat eine Affinität zu Beta-Galactosiden und weist eine antimikrobielle Aktivität gegen Bakterien und Pilze auf. Es wurde gezeigt, dass dieses Protein an den folgenden biologischen Prozessen beteiligt ist: Zelladhäsion, Zellaktivierung, Zellwachstum und Differenzierung, Zellzyklus und Apoptose. Angesichts der breiten biologischen Funktionalität von Galectin-3 wurde gezeigt, dass es an Krebs, Entzündung, Fibrose, Herzkrankheit und Schlaganfall beteiligt ist.[6][7] Studien haben auch gezeigt, dass die Expression von Galectin-3 an einer Vielzahl von Prozessen beteiligt ist, die mit Herzinsuffizienz verbunden sind, einschließlich Myofibroblasten-Proliferation, Fibrogenese, Gewebereparatur, Entzündung und Kardiales Remodeling..[6][8][9]

Galectin-3 assoziiert mit den Primären Zilien und moduliert das Nierenzystenwachstum bei angeborener polyzystischer Nierenerkrankung.[10]

Die funktionelle Rolle von Galektinen bei der zellulären Reaktion auf Membranschäden wird immer deutlicher. Kürzlich wurde gezeigt, dass Galectin-3 ESCRTs zu beschädigten Lysosomen rekrutiert, damit diese repariert werden können.[11][12][13]

Einzelnachweise

  1. ↑ Molecular cloning and chromosomal mapping of a human galactoside-binding protein. In: Cancer Research. 51. Jahrgang, Nr. 8, April 1991, S. 2173–8, PMID 2009535.
  2. ↑ Galectins. Structure and function of a large family of animal lectins. In: The Journal of Biological Chemistry. 269. Jahrgang, Nr. 33, August 1994, S. 20807–10, PMID 8063692.
  3. ↑ a b Galectin-3: an open-ended story. In: Biochimica et Biophysica Acta (BBA) - General Subjects. 1760. Jahrgang, Nr. 4, April 2006, S. 616–35.
  4. ↑ Entrez Gene: LGALS3 lectin, galactoside-binding, soluble, 3. (PMID 16478649).
  5. ↑ Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22. In: Mammalian Genome. 8. Jahrgang, Nr. 9, September 1997, S. 706–7, doi:10.1007/s003359900548, PMID 9271684.
  6. ↑ a b Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. In: Circulation. 110. Jahrgang, Nr. 19, November 2004, S. 3121–8, doi:10.1161/01.CIR.0000147181.65298.4D, PMID 15520318.
  7. ↑ Galectin-3 mediates post-ischemic tissue remodeling. In: Brain Research. 1288. Jahrgang, September 2009, S. 116–24, PMID 19573520.
  8. ↑ N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. In: American Journal of Physiology. Heart and Circulatory Physiology. 296. Jahrgang, Nr. 2, Februar 2009, S. H404–12, doi:10.1152/ajpheart.00747.2008, PMID 19098114, PMC 2643891 (freier Volltext).
  9. ↑ The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients. In: Clinica Chimica Acta; International Journal of Clinical Chemistry. 409. Jahrgang, Nr. 1–2, November 2009, S. 96–9, doi:10.1016/j.cca.2009.09.001, PMID 19747906.
  10. ↑ Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease. In: The American Journal of Pathology. 169. Jahrgang, Nr. 6, Dezember 2006, S. 1925–38, doi:10.2353/ajpath.2006.060245, PMID 17148658, PMC 1762475 (freier Volltext).
  11. ↑ Galectins Control mTOR in Response to Endomembrane Damage. In: Molecular Cell. 70. Jahrgang, Nr. 1, April 2018, S. 120–135.e8, doi:10.1016/j.molcel.2018.03.009, PMID 29625033, PMC 5911935 (freier Volltext).
  12. ↑ Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal. In: Developmental Cell. 52. Jahrgang, Nr. 1, Januar 2020, S. 69–87.e8, doi:10.1016/j.devcel.2019.10.025, PMID 31813797, PMC 6997950 (freier Volltext).
  13. ↑ AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System. In: Molecular Cell. 77. Jahrgang, Nr. 5, Januar 2020, S. 951–969.e9, doi:10.1016/j.molcel.2019.12.028, PMID 31995728, PMC 7785494 (freier Volltext).
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