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	Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling
	Zhang, Lei; Xu, Xuan; Yang, Ruhao; Chen, Jingwen; Wang, Shixuan; Yang, Junqin; Xiang, Xudong; He, Zhibiao; Zhao, Yu; Dong, Zheng
刊名	Drug Design, Development and Therapy
	2015
卷号	9页码:2139-2148
关键词	Recent studies have demonstrated that paclitaxel might inhibit renal fibrosis. However the underlying molecular mechanism remains unclear. In this study we hypothesized that low-dose paclitaxel may block the STAT3 (signal transducer and activator of transcription 3) signaling to attenuate fibrosis in a mouse model with unilateral ureteral obstruction. Both NRK-49F cells and mice with unilateral ureteral obstruction were treated with paclitaxel. The results showed that paclitaxel treatment resulted in a dose- and time-dependent decrease in tyrosine-phosphorylated STAT3 and inhibited the expression of fibronectin alpha-smooth muscle actin (α-SMA) and collagen I in cultured NRK-49F cells. S3I-201 an STAT3 inhibitor also suppressed the expression of fibronectin α-SMA and collagen I in cultured NRK-49F cells. Mechanistically paclitaxel treatment blocked the STAT3 activity by disrupting the association of STAT3 with tubulin and inhibiting STAT3 nucleus translocation. Furthermore paclitaxel also ameliorated renal fibrosis by down-regulating the expression of fibronectin α-SMA and collagen I and suppressed the infiltration of macrophages and production of TNF-α IL-1β TGF-β and ICAM-1 (intercellular adhesion molecule 1) by inhibition of STAT3 activity in obstructive nephropathy. These results suggest that paclitaxel may block the STAT3 activity by disrupting the association of STAT3 with tubulin and inhibiting STAT3 nucleus translocation consequently leading to the suppression of renal interstitial fibroblast activation and the development of renal fibrosis and inhibition of proinflammatory cytokine production.
ISSN号	1177-8881
DOI	10.2147/DDDT.S81390
URL标识	查看原文
WOS记录号	WOS:000365968900001
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/3318838
专题	中南大学
作者单位	1.[Yang, Ruhao 2.Xiang, Xudong 3.Zhang, Dongshan 4.Chen, Jingwen 5.Xu, Xuan 6.He, Zhibiao 7.Zhang, Lei] Cent S Univ, Xiangya Hosp 2, Dept Emergency Med, Changsha 410011, Hunan, Peoples R China.
推荐引用方式 GB/T 7714	Zhang, Lei,Xu, Xuan,Yang, Ruhao,et al. Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling[J]. Drug Design, Development and Therapy,2015,9:2139-2148.
APA	Zhang, Lei.,Xu, Xuan.,Yang, Ruhao.,Chen, Jingwen.,Wang, Shixuan.,...&Zhang, Dongshan*.(2015).Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling.Drug Design, Development and Therapy,9,2139-2148.
MLA	Zhang, Lei,et al."Paclitaxel attenuates renal interstitial fibroblast activation and interstitial fibrosis by inhibiting STAT3 signaling".Drug Design, Development and Therapy 9(2015):2139-2148.

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