The purpose of this review was to analyse literature on the role of galectin-3 (Gal-3) in the development of nephropathy. We searched for published and unpublished data using Pubmed as the search engine by the keywords: galectin, galectin-3, galectin-3 function, galectin-3 structure, chronic kidney disease, taking into consideration studies conducted in the last 10 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 257 analyzed articles, the findings of the researchers covered in 28 articles were crucial. In this review, we discuss the general characteristics and functions of galectin-3. There are now 15 different galectins, which were characterized and numbered according to their opening order. Gal-3 is a 32–35-kDa multifunctional lectin protein expressed by epithelial, endothelial cells and macrophages. Gal-3 is mainly secreted in the cytoplasm, extracellularly or intranuclearly. The extracellular Gal-3 modulates important interactions between epithelial cells and the extracellular matrix and plays certan role in the embryonic development of kidney ducts. The intracellular Gal-3 is important for cell survival because of its ability to block its own apoptotic pathway, and intracellular Gal-3 promotes cell proliferation. Cell adhesion and proliferation due to Gal-3 can be transformed into pathological processes such as fibrosis and cancer progression. More specifically, we focus on the role of galectin-3 in the onset and development of nephropathies. The analysis of experimental and clinical studies is carried out. Due to its multifunctional character, galectin-3 plays a pivotal role in interstitial fibrosis and progression of chronic kidney disease. Gal-3 can probably not be used as a diagnostic (screening) biomarker for chronic kidney disease due to lack of sensitivity and specificity, but may has the potential to predict progressive renal dysfunction.

galectin-3; nephropathy; review

Dumic J, Dabelic S, Flogel M. Galectin-3: an open ended story. Biochim Biophys Acta. 2006 Apr;1760(4):616-35. doi: 10.1016/j.bbagen.2005.12.020.

Vijayakumar S, Peng H, Schwartz GJ. Galectin-3 mediates oligomerization of secreted hensin using its carbohydrate-recognition domain. Am J Physiol Renal Physiol. 2013 Jul 1;305(1):F90-9. doi: 10.1152/ajprenal.00498.2012.

Desmedt V, Desmedt S, Delanghe JR, Speeckaert R, Speeckaert MM.   Galectin-3 in Renal Pathology: More Than Just an Innocent Bystander? Am J Nephrol. 2016;43(5):305-17. doi: 10.1159/000446376.

Funasaka T, Balan V, Raz A, Wong RW. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking. Biochem Biophys Res Commun. 2013 Apr 26;434(1):155-61. doi: 10.1016/j.bbrc.2013.03.052.

Hönig E, Schneider K, Jacob R. Recycling of galectin-3 in epithelial cells. Eur J Cell Biol. 2015 Jul-Sep;94(7-9):309-15. doi: 10.1016/j.ejcb.2015.05.004.

Pugliese G, Iacobini C, Ricci C, Blasetti Fantauzzi C, Menini S. Galectin-3 in diabetic patients. Clin Chem Lab Med. 2014 Oct;52(10):1413-23. doi: 10.1515/cclm-2014-0187.

Dange MC, Agarwal AK, Kalraiya RD. Extracellular galectin-3 induces MMP9 expression by activating p38 MAPK pathway via lysosome-associated membrane protein-1 (LAMP1). Mol Cell Biochem. 2015 Jun;404(1-2):79-86. doi: 10.1007/s11010-015-2367-5.

Thomas L, Pasquini LA. Extracellular Galectin-3 Induces accelerated oligodendroglial differentiation through changes in signaling pathways and cytoskeleton dynamics. Mol Neurobiol. 2019 Jan;56(1):336-349. doi: 10.1007/s12035-018-1089-6.

Iacobini C, Fantauzz CB, Pugliese G, Menini S. Role of galectin-3 in bone cell differentiation, bone pathophysiology and vascular osteogenesis. Int J Mol Sci. 2017 Nov 21;18(11). pii: E2481. doi: 10.3390/ijms18112481.

Itabashi T, Arima Y, Kamimura D, et al. Cell- and stage-specific localization of galectin-3, a β-galactoside-binding lectin, in a mouse model of experimental autoimmune encephalomyelitis. Neurochem Int. 2018 Sep;118:176-184. doi: 10.1016/j.neuint.2018.06.007.

de Boer RA, van Veldhuisen DJ, Gansevoort RT, et al. The fibrosis marker galectin-3 and outcome in the general population. J Intern Med. 2012 Jul;272(1):55-64. doi: 10.1111/j.1365-2796.2011.02476.x.

Danella Polli C, Alves Toledo K, Franco LH, et al. Monocyte Migration Driven by Galectin-3 Occurs through Distinct Mechanisms Involving Selective Interactions with the Extracellular Matrix. ISRN Inflamm. 2013 Feb 25;2013:259256. doi: 10.1155/2013/259256.

Koca SS, Akbas F, Ozgen M, et al. Serum galectin-3 level in systemic sclerosis. Clin Rheumatol. 2014 Feb;33(2):215-20. doi: 10.1007/s10067-013-2346-8.

Yabuta C, Yano F, Fujii A, Shearer TR, Azuma M. Galectin-3 enhances epithelial cell adhesion and wound healing in rat cornea. Ophthalmic Res. 2014;51(2):96-103. doi: 10.1159/000355846.

Li LC, Li J, Gao J. Functions of galectin-3 and its role in fibrotic diseases. J Pharmacol Exp Ther. 2014 Nov;351(2):336-43. doi: 10.1124/jpet.114.218370.

von Mach T, Carlsson MC, Straube T, Nilsson U, Leffler H, Jacob R. Ligand binding and complex formation of galectin-3 is modulated by pH variations. Biochem J. 2014 Jan 1;457(1):107-15. doi: 10.1042/BJ20130933.

Pugliese G, Iacobini C, Pesce CM, Menini S. Galectin-3: an emerging all-out player in metabolic disorders and their complications. Glycobiology. 2015 Feb;25(2):136-50. doi: 10.1093/glycob/cwu111. 

Thomas L, Pasquini LA. Galectin-3-Mediated Glial Crosstalk Drives Oligodendrocyte Differentiation and (Re)myelination. Front Cell Neurosci. 2018 Sep 12;12:297. doi: 10.3389/fncel.2018.00297.

Li LC, Li J, Gao J. Functions of Galectin-3 and Its Role in Fibrotic Diseases. J Pharmacol Exp Ther. 2014 Nov;351(2):336-43. doi: 10.1124/jpet.114.218370.

Bänfer S, Schneider D, Dewes J, et al. Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion. Proc Natl Acad Sci U S A. 2018 May 8;115(19):E4396-E4405. doi: 10.1073/pnas.1718921115.

Brittoli A, Fallarini S, Zhang H, Pieters RJ, Lombardi G. “In vitro” studies on galectin-3 in human natural killer cells. Immunol Lett. 2018 Feb;194:4-12. doi: 10.1016/j.imlet.2017.12.004.

Zhou W, Chen X, Hu Q, Chen X, Chen Y, Huang L. Galectin-3 activates TLR4/NF-κB signaling to promote lung adenocarcinoma cell proliferation through activating lncRNA-NEAT1 expression. BMC Cancer. 2018 May 22;18(1):580. doi: 10.1186/s12885-018-4461-z.

Haudek KC, Spronk KJ, Voss PG, Patterson RJ, Wang JL, Arnoys EJ. Dynamics of galectin-3 in the nucleus and cytoplasm. Biochim Biophys Acta. 2010 Feb;1800(2):181-9. doi: 10.1016/j.bbagen.2009.07.005.

Téllez-Sanz R, García-Fuentes L, Vargas-Berenguel A. Human galectin-3 selective and high affinity inhibitors. Present state and future perspectives. Curr Med Chem. 2013;20(24):2979-90.

de Boer RA, Edelmann F, Cohen-Solal A, Mamas MA, Maisel A, Pieske B. Galectin-3 in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013 Oct;15(10):1095-101. doi: 10.1093/eurjhf/hft077.

Ho JE, Liu C, Lyass A, et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol. 2012 Oct 2;60(14):1249-56. doi: 10.1016/j.jacc.2012.04.053.

Anand IS, Rector TS, Kuskowski M, Adourian A, Muntendam P, Cohn JN. Baseline and serial measurements of galectin-3 in patients with heart failure: relationship to prognosis and effect of treatment with valsartan in the Val-HeFT. Eur J Heart Fail. 2013 May;15(5):511-8. doi: 10.1093/eurjhf/hfs205.

Traber PG, Chou H, Zomer E, et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One. 2013 Oct 9;8(10):e75361. doi: 10.1371/journal.pone.0075361.

Chen SC, Kuo PL. The Role of Galectin-3 in the Kidneys. Int J Mol Sci. 2016 Apr 14;17(4):565. doi: 10.3390/ijms17040565.

Dang Z, MacKinnon A, Marson LP, Sethi T. Tubular atrophy and interstitial fibrosis after renal transplantation is dependent on galectin-3. Transplantation. 2012 Mar 15;93(5):477-84. doi: 10.1097/TP.0b013e318242f40a.

Kariya Y, Oyama M, Hashimoto Y, Gu J, Kariya Y. β4-Integrin/PI3K signaling promotes tumor progression through the galectin-3-N-glycan complex. Mol Cancer Res. 2018 Jun;16(6):1024-1034. doi: 10.1158/1541-7786.MCR-17-0365.

Ruvolo PP. Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta. 2016 Mar;1863(3):427-437. doi: 10.1016/j.bbamcr.2015.08.008.

Hu K, Gu Y, Lou L, et al. Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway. J Hematol Oncol. 2015 Jan 27;8:1. doi: 10.1186/s13045-014-0099-8.

McLeod K, Walker JT, Hamilton DW. Galectin-3 regulation of wound healing and fibrotic processes: insights for chronic skin wound therapeutics. J Cell Commun Signal. 2018 Mar;12(1):281-287. doi: 10.1007/s12079-018-0453-7.

More SK, Chiplunkar SV, Kalraiya RD. Galectin-3-induced cell spreading and motility relies on distinct signaling mechanisms compared to fibronectin. Mol Cell Biochem. 2016 May;416(1-2):179-91. doi: 10.1007/s11010-016-2706-1.

Nishihara H, Shimizu F, Kitagawa T, et al. Identification of galectin-3 as a possible antibody target for secondary progressive multiple sclerosis. Mult Scler. 2017 Mar;23(3):382-394. doi: 10.1177/1352458516655217.

Savic J, Zeljkovic A, Bogavac-Stanojevic N, et al. Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease. Scand J Clin Lab Invest. 2014 Oct;74(7):637-43. doi: 10.3109/00365513.2014.928944.

Bansal N, Katz R, Seliger S, et al. Galectin-3 and soluble ST2 and kidney function decline in older adults: the Cardiovascular Health Study (CHS). Am J Kidney Dis. 2016 Jun;67(6):994-6. doi: 10.1053/j.ajkd.2015.12.022.

Iacoviello M, Aspromonte N, Leone M, et al. Galectin-3 serum levels are independently associated with microalbuminuria in chronic heart failure outpatients. Res Cardiovasc Med. 2015 Dec 14;5(1):e28952. doi: 10.5812/cardiovascmed.28952.

O’Seaghdha CM, Hwang SJ, Ho JE, Vasan RS, Levy D, Fox CS. Elevated galectin-3 precedes the development of CKD. J Am Soc Nephrol. 2013 Sep;24(9):1470-7. doi: 10.1681/ASN.2012090909. 

Calvier L, Miana M, Reboul P, et al. Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):67-75. doi: 10.1161/ATVBAHA.112.300569.

Rahimian R, Béland LC, Kriz J. Galectin-3: mediator of microglia responses in injured brain. Drug Discov Today. 2018 Feb;23(2):375-381. doi: 10.1016/j.drudis.2017.11.004.

Martinez-Martinez E, Ibarrola J, Calvier L, et al. Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage. PLoS One. 2016 Nov 9;11(11):e0166272. doi: 10.1371/journal.pone.0166272.

Bertocchi AP, Campanhole G, Wang PH, et al. A Role for galectin‐3 in renal tissue damage triggered by ischemia and reperfusion injury Journal compilation. Transpl Int. 2008 Oct;21(10):999-1007. doi: 10.1111/j.1432-2277.2008.00705.x.

Kinnon M, Farnworth SL, Hodkinson PS, et al. Regulation of Alternative Macrophage Activation by Galectin-31 Alison C. J Immunol. 2008 Feb 15;180(4):2650-8. doi: 10.4049/jimmunol.180.4.2650.

Kikuchi K, Tancharoen S, Ito T, et al. Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke. Int J Mol Sci. 2013 Sep 13;14(9):18899-924. doi: 10.3390/ijms140918899.

Kang EH, Moon KC, Lee EY, et al. Renal expression of galectin-3 in systemic lupus erythematosus patients with nephritis. Lupus. 2009 Jan;18(1):22-8. doi: 10.1177/0961203308094361.

Sun Z, Ma Ch, Jin H, Yuan Y, Liu NF. Effects of advanced glycosylation end products and rosiglitazone on the expression and secretion of galectin-3 in human renal mesangial cells. Chin Med J (Engl). 2009 May 5;122(9):1067-71.

Tampe D, Zeisberg M. Potential approaches to reverse or repair renal fibrosis. Nat Rev Nephrol. 2014 Apr;10(4):226-37. doi: 10.1038/nrneph.2014.14.

Tokarchuk NI, Odarchuk IV. The comparative characteristic of indicators of activity of inflammatory process with pyelonephritis on the background of vesicoureteral reflux in children of early age. Journal of Education, Health and Sport. 2016;6(8):734-746. doi: 10.5281/zenodo.62073. (in Russian).

Tokarchuk NI, Odarchuk IV, Vyzhha YV, Antonec TI, Starinec LS. Characteristics of the galectin 3 indicators in pyelonephritis on the background of the vesiculo-uretral reflexes in children of early age. Neonatology, Surgery and Perinatal Medicine. 2017;7(3):68-74. doi: 10.24061/2413-4260.VII.3.25.2017.11. (in Ukrainian).