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
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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 |
DOI | 10.1186/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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