Attenuation of Tubular Injury and Renal Fibrosis by TI-HU-YIN via Reduction in Transforming Growth Factor-β1 Expression in Unilateral Ureteral Obstruction Mice

Der-Cherng Tarng ； I-Shan Liu ； Lie-Chwen Lin ； Nien-Jung Chen

《The Chinese Journal of Physiology》 58卷6期 (2015/12) Pp. 367-376

https://doi.org/10.4077/CJP.2015.BAD326

並列摘要

TI-HU-YIN (JCKD), a compound composed of many Chinese herbs, is hypothesized to attenuate renal tubular injury and interstitial fibrosis. Moreover, its renoprotective effects were assessed in animal and in vitro studies. First, male C57BL/6 mice were under sham operation or unilateral ureteral obstruction (UUO) surgery, and then treated with phosphate buffer solution (PBS), aliskirin and valsartan (A+V), and JCKD for 14 days. At 7 and 14 days, mice were sacrificed and the kidney tissues were assessed for histopathological changes and transforming growth factor (TGF)-β1 expression. As compared to sham group, UUO-PBS group had more serious tubular dilatation and injury, α-smooth muscle actin-positive areas, F4/80-positive macrophages, and interstitial fibrosis. Impressively, these pathologic changes were significantly attenuated in UUO mice both treated with JCKD and A+V as compared to UUO-PBS group. At 14 days, TGF-β1 expression was significantly suppressed in kidney tissues of UUOJCKD group as well as in UUO-A+V group. Second, TGF-β1 production was increased in macrophage J774 cells and NRK-52E proximal tubular cells stimulated by angiotensin (Ang)-II at 10 nM for 24 h and at 1 nM for 48 h, respectively. JCKD (≥ 400 μg/ml) inhibited the TGF-β1 production at baseline and stimulated by Ang II in both cell lines. Our study showed that JCKD reduced renal injury, macrophage infiltration and interstitial fibrosis possibly through suppressing the TGF-β1 expression in UUO mice. Accordingly, JCKD is potential to retard the progression of chronic kidney disease. Further studies are needed to validate its renoprotective effects in the inhibition of TGF-β1 expression and the amelioration of renal fibrosis.

並列關鍵字

angiotensin II ； Chinese herbs ； kidney injury ； renal fibrosis ； transforming growth factor-β1 ； unilateral ureteral obstruction

參考文獻

Butz, H.,Racz, K.,Hunyady, L.,Patocs, A.(2012).Crosstalk between TGF-β signaling and the microRNA machinery.Trends Pharmacol. Sci..33,382-393.

Cao, Q.,Wang, C.,Zheng, D.,Wang, Y.,Lee, V. W.,Wang, Y. M.,Zheng, G.,Tan, T. K.,Yu, D.,Alexander, S. I.,Harris, D. C.,Wang, Y.(2011).IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney disease.J. Am. Soc. Nephrol.22,1229-1239.

Cheng, C. C.,Lin, N. N.,Lee, Y. F.,Wu, L. Y.,Hsu, H. P.,Lee, W. J.,Tung, K. C.,Chiun, Y. T.(2010).Effects of Shugan-Huayu powder, a traditional Chinese medicine, on hepatic fibrosis in rat model.Chinese J. Physiol.53,223-233.

Chevalier, R. L.,Forbes, M. S.,Thornhill, B. A.(2009).Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy.Kidney Int..75,1145-1152.

de Paula, R. B.,da Silva, A. A.,Hall, J. E.(2004).Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration.Hypertension.43,41-47.