Early growth response factor 1 upregulates pro-fibrotic genes through activation of TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in high-glucose treated HK-2 cells.

ABSTRACT

Tubulointerstitial fibrosis (TIF) makes a key role in diabetic kidney disease (DKD). In this study, we revealed that the expressions of Egr1 and protease-activated receptor 1 (PAR1) were increased in renal tissues of DKD rats. In vitro experiments demonstrated that both Egr1 overexpression and high glucose (HG) condition could promote the expressions of PAR1, fibronectin (FN) and collagen I (COL I). Furthermore, HG stimulation enhanced the binding capacity of Egr1 to PAR1 promoter. Both HG condition and Egr1 upregulation could increase, and thrombin inhibitor did not affect activity of TGF-ß1/Smad pathway via PAR1. Collectively, Egr1 is involved in TIF of DKD partly through activating TGF-ß1/Smad pathway via transcriptional regulation of PAR1 in HG treated HK-2 cells.