[Role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney diseases].

OBJECTIVE: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis 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 infiltration of mast cells in the kidneys of DKD rats. The expression of α-SMA in the kidneys of DKD rats inereased significantly (P<0.05), while the expression of E-cadherin decreased (P<0.05). Tranilast increased the expression of E-cadherin and decreased the expression of α-SMA in the prophase of DKD dose dependently. The expressions of FN and Col I were increased in the tubulointerstitial fields in DKD model rats (P<0.05). After the tranilast treatment, these changes were relieved to a certein degree (P<0.05). The expression of SCF and c-kit in the tubular and interstitial tissue was slight. The increased expressions of SCF and c-kit protein and mRNA in DKD model rats were downregulated by tranilat (P<0.05). The expressions of SCF and c-kit were positively correlated with the infiltration degree of mast cells and the expressions of FN, Col I.

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 infiltration of mast cells induced by SCF/c-kit pathway.