Role and mechanism of tranilast preventing the progression of tubulointerstilial ifbrosis in diabetic kidney diseases / 中南大学学报(医学版)

ABSTRACT

Objective:To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial ifbrosis in diabetic kidney disease (DKD). Methods:Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin,α-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin,α-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. Results:Tranilast can inhibit the inifltration of mast cells in the kidneys of DKD rats. The expression ofα-SMA in the kidneys of DKD rats inereased signiifcantly (P Conclusion:Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the inifltration of mast cells induced by SCF/c-kit pathway.