Abstract
Transforming growth factor (TGF-β1) 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 α2(I) collagen (COL1A2) in TGF-β1- 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-β1-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-β1-stimulated renal epithelial cells.
Original language | English (US) |
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Pages (from-to) | 3304-3311 |
Number of pages | 8 |
Journal | Cellular and Molecular Life Sciences |
Volume | 65 |
Issue number | 20 |
DOIs | |
State | Published - Oct 2008 |
Externally published | Yes |
Funding
Keywords
- Galectin-1
- Renal fibrosis
- SBE
- Smad3
- TGF-β1
- Type I collagen
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Cellular and Molecular Neuroscience
- Cell Biology