Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation-related signalling pathways

doi:10.1111/bph.14842

科研成果详情

题名	Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation-related signalling pathways
作者	Zhang, Xing1,2; Lu, Hong3; Xie, Shuangshuang 2; Wu, Cunzao4; Guo, Yangyang1; Xiao, Yanyi 1; Zheng, Shizhang 1; Zhu, Hengyue 1; Zhang, Yan 4,5; Bai, Yongheng1,5
发表日期	2019-12
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	RENAL INTERSTITIAL FIBROSIS ; GROWTH-FACTOR-BETA ; EPITHELIAL-MESENCHYMAL TRANSITION ; TGF-BETA ; TUBULOINTERSTITIAL FIBROSIS ; DIABETIC-NEPHROPATHY ; GENE-EXPRESSION ; DIVERSE ROLES ; CONCISE GUIDE ; IN-VIVO
摘要	Background and Purpose Renal fibrosis acts as the common pathway leading to the development of end-stage renal disease. Previous studies have shown that resveratrol has anti-fibrotic activity, but its potential molecular mechanisms of action are not well understood. Experimental Approach The anti-fibrotic effects of resveratrol were assayed in a rat model of unilateral ureteral obstruction (UUO) in vivo and in fibroblasts and tubular epithelial cells (TECs) stimulated by TGF-beta 1 in vitro. Gene and protein expression levels were analysed by PCR, Western blotting, and immunohistochemical staining. Key Results Resveratrol inhibits the myofibroblastic phenotype and fibrosis formation in UUO kidneys by targeting fibroblast-myofibroblast differentiation (FMD) and epithelial-mesenchymal transition (EMT). The anti-fibrotic effects of resveratrol correlated with decreased proliferation of TECs in the interstitium and tubules, resulting in suppressed activity of the proliferation-related signalling pathways, including that of the MAPK, PI3K/Akt, Wnt/beta-catenin, and JAK2/STAT3 pathways. Resveratrol treatment suppressed TGF-beta 1-induced FMD and the expression of the myofibroblastic phenotype in fibroblasts in vitro by antagonizing the activation of proliferation-related signalling. Similarly, TGF-beta 1-mediated overactivation of the proliferation-related signalling in TECs induced EMT, and the myofibroblastic phenotype was suppressed by resveratrol. The anti-fibrotic and anti-proliferative effects of resveratrol were associated with the inactivation of Smad2/3 signalling and resulted in a partial reversal of FMD and EMT and the inhibition of the myofibroblastic phenotype. Conclusions and Implications Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in vivo and in vitro via proliferation-related pathways, making it a potential therapeutic agent for preventing renal fibrosis.
资助项目	Wenzhou Municipal Science and Technology Plan Project [Y20190124]; Natural Science Foundation of Zhejiang Province, ChinaNatural Science Foundation of Zhejiang Province [LY17H050005]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772264]
出版者	WILEY
出版地	HOBOKEN
ISSN	0007-1188
EISSN	1476-5381
卷号	176 期号:24 页码:4745-4759
DOI	10.1111/bph.14842
页数	15
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000498878200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31454852
PMC记录号	PMC6965682
SCOPUSEID	2-s2.0-85075744664
自科自定义期刊分类	T3(B)类
通讯作者地址	[Bai, Yongheng]Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology
引用统计	被引频次：27[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17291
专题	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室检验医学院（生命科学学院、生物学实验教学中心）附属第一医院_移植科
通讯作者	Bai, Yongheng
作者单位	1.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Zhejiang University School of Medicine,Hangzhou,China; 3.Department of Laboratory Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 4.Department of Transplantation,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 5.Institute of Kidney Health,Center for Health Assessment,Wenzhou Medical University,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhang, Xing,Lu, Hong,Xie, Shuangshuang,et al. Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation-related signalling pathways[J]. BRITISH JOURNAL OF PHARMACOLOGY,2019,176(24):4745-4759.
APA	Zhang, Xing., Lu, Hong., Xie, Shuangshuang., Wu, Cunzao., Guo, Yangyang., ... & Bai, Yongheng. (2019). Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation-related signalling pathways. BRITISH JOURNAL OF PHARMACOLOGY, 176(24), 4745-4759.
MLA	Zhang, Xing,et al."Resveratrol suppresses the myofibroblastic phenotype and fibrosis formation in kidneys via proliferation-related signalling pathways".BRITISH JOURNAL OF PHARMACOLOGY 176.24(2019):4745-4759.