Petchiether A attenuates obstructive nephropathy by suppressing TGF-ss/Smad3 and NF-kappa B signalling

doi:10.1111/jcmm.14454

	Petchiether A attenuates obstructive nephropathy by suppressing TGF-ss/Smad3 and NF-kappa B signalling
	You, Yong-Ke 1,2; Luo, Qi3 ; Wu, Wei-Feng 1; Zhang, Jiao-Jiao 4; Zhu, Hong-Jian 5; Lao, Lixing 1,2; Lan, Hui Y.6,7; Chen, Hai-Yong 1,2; Cheng, Yong-Xian 3,4
通讯作者	Chen, Hai-Yong(haiyong@hku.hk) ; Cheng, Yong-Xian(yxcheng@szu.edu.cn)
	2019-08-01
发表期刊	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷号	23 期号:8 页码:5576-5587
摘要	Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor-ss 1 (TGF-ss 1)/Smad3-driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small-molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF-ss 1-induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin-1 ss and tumour necrosis factor-alpha) and reducing extracellular matrix deposition (alpha-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-kappa B p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down-regulated the expression of the fibrotic marker collagen I in TGF-ss 1-treated renal epithelial cells. Further, we found that petA dose-dependently suppressed Smad3-responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF-ss/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF-ss/Smad3 signalling.
关键词	fibrosis NF-kappa B obstructive nephropathy petchiether A TGF-ss/Smad3
DOI	10.1111/jcmm.14454
收录类别	SCI
语种	英语
WOS记录号	WOS:000481532600066
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/68353
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Chen, Hai-Yong; Cheng, Yong-Xian
作者单位	1.Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, Hong Kong, Peoples R China 2.Univ Hong Kong, Shenzhen Hosp, Dept Chinese Med, Shenzhen, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China 4.Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Guangdong Key Lab Genome Stabil & Dis Prevent, Shenzhen, Peoples R China 5.Univ Melbourne, Dept Surg, Melbourne, Vic, Australia 6.Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China 7.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China
推荐引用方式 GB/T 7714	You, Yong-Ke,Luo, Qi,Wu, Wei-Feng,et al. Petchiether A attenuates obstructive nephropathy by suppressing TGF-ss/Smad3 and NF-kappa B signalling[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2019,23(8):5576-5587.
APA	You, Yong-Ke.,Luo, Qi.,Wu, Wei-Feng.,Zhang, Jiao-Jiao.,Zhu, Hong-Jian.,...&Cheng, Yong-Xian.(2019).Petchiether A attenuates obstructive nephropathy by suppressing TGF-ss/Smad3 and NF-kappa B signalling.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,23(8),5576-5587.
MLA	You, Yong-Ke,et al."Petchiether A attenuates obstructive nephropathy by suppressing TGF-ss/Smad3 and NF-kappa B signalling".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 23.8(2019):5576-5587.

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