Cell-specific regulation of alpha1(III) and alpha2(V) collagen by TGF-beta1 in tubulointerstitial cell models

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
R BertelliG M Ghiggeri

Abstract

TGF-beta1 modulates the cellular expression of extracellular matrix (ECM) in several renal cell systems in vitro and is considered a determinant of ECM accumulation in tubulointerstitial fibrosis. We evaluated the effects of TGF-beta1 on collagen transcription, expression, and removal of the relevant collagens by rat tubuloepithelial cells (NRK 52E) and both rat and monkey interstitial fibroblasts (NRK 49F, CV1) in vitro. TGF-beta1 upregulated the expression of alpha1(III) collagen by fibroblasts (+300%) without affecting its removal. In parallel, a threefold increment of COL3A1 mRNA was found. Experiments of cell transfection employing CV1 fibroblasts as the unique suitable model, and chimaeric constructs of COL3A1 and COL5A2 promoters fused to the luciferase reporter gene, demonstrated a twofold stimulation of a large 1436 COL3A1 promoter construct and negligible effects on shorter fragments, suggesting the presence of a positive responsive element in a region of COL3A1 promoter between -1375 and -579. TGF-beta1 did not influence COL5A2 mRNA and the relative promoter activity in renal fibroblasts. With NRK 52E cell line, TGF-beta1 induced comparable increment of both alpha1(III) collagen expression (+300%) and COL3A1 mRNA (+3...Continue Reading

Citations

Feb 10, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Narasimhaswamy S BelaguliDavid H Berger
Aug 28, 2001·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·B A YardF J van der Woude
Jun 1, 2000·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·R OlegginiG M Ghiggeri
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