ABSTRACT
Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage kidney disease. Previous studies showed that upregulation of TGFbeta1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction. This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the rodent model of chronic renal failure involving 5/6 nephrectomy. The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model. Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group, but the lesion was attenuated mostly in irbesartan-treated group. Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFbeta1 which was up-regulated in operation groups. Western blot showed that irbesartan treatment down-regulated the expression of TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38) MAPK, but significantly up-regulated the protein expression of smad6 as compared with operation group. These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.
ABSTRACT
AIM:to investigate the effects of extract of ginkgo biloba (EGB) on human tubular epithelial-mesenchymal transition induced by transforming growth factor-?1.METHODS: HK2 cells were induced to epithelial-mesenchymal transition by transforming growth factor-?1 (TGF-?1, 10 ?g/L). EGB was added into the medium of HK2 cells 2 h before TGF-?1 was added. The expressions of E-cadherin, ?-smooth muscle actin (?-SMA), NADPH oxidase p67phox and superoxide dismutase (SOD) were determined by Western blotting. Malondialdehyde (MDA) in the mediums of HK2 cells was detected. RESULTS: EGB significantly attenuated the downregulation of E-cadherin, the upregulation of ?-SMA and p67phox, the downregulation of SOD and the upregulation of MDA in HK2 cells induced by TGF-?1.CONCLUSION: EGB significantly attenuates human tubular epithelial-mesenchymal transition induced by TGF-?1, and its underlying mechanism is that EGB attenuates the upregulation of p67phox and the downregulation of SOD induced by TGF-?1.