title: The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine.
abstract: Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals1(-/-)) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals1(-/-) mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function.
authors: Laboratorio de Investigaciones del Sistema Inmune, Facultad de Ciencias Exactas, Universidad de La Plata, La Plata, Argentina.
authors: C
authors: C
authors: Muglia
authors: N
authors: N
authors: Mercer
authors: M A
authors: MA
authors: Toscano
authors: M
authors: M
authors: Schattner
authors: R
authors: R
authors: Pozner
authors: J P
authors: JP
authors: Cerliani
authors: R Papa
authors: RP
authors: Gobbi
authors: G A
authors: GA
authors: Rabinovich
authors: G H
authors: GH
authors: Docena
references: Immunol Rev. 2009 Jul;230(1):144-59
references: 19594634
references: Proc Natl Acad Sci U S A. 1979 Apr;76(4):1962-6
references: 287037
references: FASEB J. 2008 Mar;22(3):682-90
references: 17965266
references: J Biol Chem. 2005 Feb 25;280(8):6969-85
references: 15556941
references: J Clin Pathol. 1992 May;45(5):416-9
references: 1350788
references: BMC Cancer. 2009 Sep 28;9:347
references: 19785749
references: J Histochem Cytochem. 2009 Jan;57(1):41-50
references: 18796404
references: Anticancer Res. 2005 May-Jun;25(3A):1575-80
references: 16033063
references: Gastroenterology. 2004 Jul;127(1):213-23
references: 15236187
references: Gastroenterology. 1997 Dec;113(6):1906-15
references: 9394730
references: Cancer Cell Int. 2001 Dec 17;1(1):2
references: 11983026
references: Dig Dis Sci. 2003 Apr;48(4):765-9
references: 12741469
references: Biochem Biophys Res Commun. 1993 Nov 30;197(1):40-5
references: 8250945
references: Clin Exp Immunol. 2010 Oct;162(1):108-15
references: 20731675
references: J Pathol. 2008 May;215(1):1-12
references: 18335458
references: Gastroenterology. 2003 May;124(5):1381-94
references: 12730878
references: Curr Opin Cell Biol. 1994 Dec;6(6):795-803
references: 7880525
references: J Mol Med (Berl). 2008 Dec;86(12):1395-406
references: 18064431
references: Nat Rev Immunol. 2009 May;9(5):338-52
references: 19365409
references: Immunol Lett. 2010 Jan 4;127(2):108-18
references: 19874850
references: J Immunol. 2006 May 15;176(10):6323-32
references: 16670344
references: Int J Cancer. 2003 Jan 20;103(3):370-9
references: 12471620
references: J Cell Mol Med. 2010 Jan;14(1-2):165-74
references: 19627399
references: J Histochem Cytochem. 2005 Nov;53(11):1323-34
references: 15956024
references: Int J Oncol. 1999 Feb;14(2):225-32
references: 9917496
references: Int J Exp Pathol. 2008 Dec;89(6):438-46
references: 19134053
references: Nat Immunol. 2009 Sep;10(9):981-91
references: 19668220
references: Methods Mol Biol. 2011;677:355-74
references: 20941621
references: Eur J Cancer. 1999 Jun;35(6):978-83
references: 10533482
references: Gastroenterology. 2005 Aug;129(2):550-64
references: 16083712
references: Nat Rev Immunol. 2003 Apr;3(4):331-41
references: 12669023
references: Int J Immunopathol Pharmacol. 2009 Jan-Mar;22(1):207-17
references: 19309568
references: J Cell Mol Med. 2001 Jul-Sep;5(3):327-51
references: 12067494
references: Inflamm Bowel Dis. 2008 Oct;14(10):1366-72
references: 18484670
references: Nature. 1995 Dec 14;378(6558):736-9
references: 7501023
references: Am J Clin Pathol. 2001 Apr;115(4):494-503
references: 11293896
references: Glycobiology. 2004 Feb;14(2):127-37
references: 14638631
references: Int J Colorectal Dis. 2005 May;20(3):277-86
references: 15503066
references: Nat Immunol. 2007 Aug;8(8):825-34
references: 17589510
references: J Cell Mol Med. 2005 Jan-Mar;9(1):11-24
references: 15784161
references: Gastroenterology. 2007 Aug;133(2):587-98
references: 17681178
references: Gut. 2004 Jan;53(1):70-7
references: 14684579