中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway

文献类型:期刊论文

作者Yang, Cheng1,2,8; Cao, Ye4,5; Zhang, Yi1; Li, Long1,8; Xu, Ming1,8; Long, Yaqiu6; Rong, Ruiming1,7,8; Zhu, Tongyu1,3,8
刊名Journal of Translational Medicine
出版日期2015-11-10
卷号13
关键词Cyclic helix B peptide Renal ischemia reperfusion injury Fibrosis Akt FoxO3
ISSN号1479-5876
DOI10.1186/s12967-015-0699-2
文献子类Article
英文摘要Renal fibrosis is a main cause of end-stage renal disease. Clinically, there is no beneficial treatment that can effectively reverse the progressive loss of renal function. We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. In this study, we evaluated the effect of CHBP on renal fibrosis in an in vivo ischemia reperfusion injury (IRI) model and in vitro TGF-beta-stimulated tubular epithelial cells (TCMK-1 and HK-2) model. In the IRI in vivo model, mice were randomly divided into sham (sham operation), IR and IR + CHBP groups (n = 6). CHBP (8 nmol/kg) was administered intraperitoneally at the onset of reperfusion, and renal fibrosis was evaluated at 12 weeks post-reperfusion. Our results showed that CHBP markedly attenuated the IRI-induced deposition of collagen I and vimentin. In the in vitro model, CHBP reversed the TGF-beta-induced down-regulation of E-cadherin and up-regulation of alpha-SMA and vimentin. Furthermore, CHBP inhibited the phosphorylation of Akt and Forkhead box O 3a (FoxO3a), whose anti-fibrotic effect could be reversed by the 3-phosphoinositide-dependent kinase-1 (PI3K) inhibitor wortmannin as well as FoxO3a siRNA. These findings demonstrate that CHBP attenuates renal fibrosis and the epithelial-mesenchymal transition of tubular cells, possibly through suppression of the PI3K/Akt pathway and thereby the inhibition FoxO3a activity.
WOS关键词NAKED CASPASE-3 SIRNA ; ACUTE KIDNEY INJURY ; ISCHEMIA/REPERFUSION INJURY ; AUTOTRANSPLANT KIDNEYS ; INFLAMMATION ; ACTIVATION ; DISEASE ; MODEL
资助项目National Natural Science Foundation of China[81400752] ; National Natural Science Foundation of China[81400688] ; National Natural Science Foundation of China[81270832] ; National Natural Science Foundation of China[81270833] ; National Natural Science Foundation of China[81570674] ; National Natural Science Foundation of China[81370852] ; China National Science Fund for Distinguished Young Scholars[81325020]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000364443400002
出版者BIOMED CENTRAL LTD
源URL[http://119.78.100.183/handle/2S10ELR8/276327]  
专题药物化学研究室
通讯作者Rong, Ruiming
作者单位1.Shanghai Key Lab Organ Transplantat, Shanghai 200032, Peoples R China;
2.Fudan Univ, Zhongshan Hosp, Dept Plast Surg, Shanghai 200032, Peoples R China
3.Fudan Univ, Qingpu Branch Zhongshan Hosp, Shanghai 201700, Peoples R China;
4.Shanghai Univ Chinese Tradit Med, Dept Chinese Tradit Med, Shanghai 201203, Peoples R China;
5.London Metropolitan Univ, Fac Life Sci & Comp, London N7 8DB, England;
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
7.Fudan Univ, Zhongshan Hosp, Dept Transfus, Shanghai 200032, Peoples R China;
8.Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China;
推荐引用方式
GB/T 7714
Yang, Cheng,Cao, Ye,Zhang, Yi,et al. Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway[J]. Journal of Translational Medicine,2015,13.
APA Yang, Cheng.,Cao, Ye.,Zhang, Yi.,Li, Long.,Xu, Ming.,...&Zhu, Tongyu.(2015).Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway.Journal of Translational Medicine,13.
MLA Yang, Cheng,et al."Cyclic helix B peptide inhibits ischemia reperfusion-induced renal fibrosis via the PI3K/Akt/FoxO3a pathway".Journal of Translational Medicine 13(2015).

入库方式: OAI收割

来源:上海药物研究所

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