Renal fibrosis is characterized by excessive accumulation of extracellular matrix. It is associated with a declining renal function. The molecular mechanisms of the renal fibrosis are still not completely understood. Here is demonstrated by using proteomics approaches that TGFß-1 induced transformation of the renal fibroblasts leads to an upregulation of fibrosis and myofibroblasts markers (e. g. VIM, DES, ACTA, FIN) and leads to an upregulation of ER-Stress proteins (e. g. Calreticulin, GRP78, PDI) and of proteins of the oxidative stress pathway (e. g. PRDX1, PRDX2, SOD1) . So the TGFß-1 stimulation of the renal fibroblasts leads to ER stress followed by the unfolded protein response. This results suggests that the secretion of the proteins of the ER-stress pathway is one of the early stages of renal fibrosis. It prevents the accumulation of misfolded proteins in the ER by upregulating the expression of ER chaperones. So the Overexpression of ER stress proteins might serve as a therapeutic target in renal fibrosis.
Keywords: renal fibrosis; TGFß-1; ER stress; UPR; 2D gel electrophoresis; mass spectrometry analysis
