Galectin-1 suppresses alpha2(I) collagen through Smad3 in renal epithelial cells.
Transforming growth factor (TGF-beta1) promotes renal fibrogenesis through activation of Smads. Galectin-1 is reported to prevent experimental glomerulonephritis. Here we investigated the fact that transfected galectin-1 significantly suppressed the transcription of alpha2(I) collagen (COL1A2) in TGF-beta1- activated human renal epithelial cells. Conversely, galectin-1 silencing RNA reduced secretion of type I collagen by HKC cells. Galectin-1 significantly decreased activation of a TGF-beta1-responsive reporter construct and of a minimal reporter construct that contains four repeats of the Smad binding element (SBE). Galectin-1 had no effect on phosphorylation of Smad3 at the linker region and C-terminus, whereas it decreased affinity of Smad3 to the SBE. Additionally, the inhibitory effect of galectin-1 disappeared using a mutated reporter construct, 376 m-LUC, in which a potential Smad recognition site within the promoter is mutated. Taken together, the results suggest that galectin-1 decreases Smad3-complex from binding to the SBE, down-regulating transcription of COL1A2 in TGF-beta1-stimulated renal epithelial cells.
Okano
K
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, 162-8666, Japan. kaokano@kc.twmu.ac.jp
Uchida
K
K
Nitta
K
K
Hayashida
T
T
D001665:Binding Sites; D002460:Cell Line; D024042:Collagen Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D037483:Galectin 1 / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D007668:Kidney / Q000166:cytology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D024042:Collagen Type I; D037483:Galectin 1; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1