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Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
Tan, Xiao-Hua1; Zheng, Xiao-Meng1; Yu, Li-Xia1; He, Jian2; Zhu, Hong-Mei1; Ge, Xiu-Ping3; Ren, Xiao-Li4; Ye, Fa-Qing1; Bellusci, Saverio5,6; Xiao, Jian1; Li, Xiao-Kun1,5; Zhang, Jin-San1,5
关键词Fibroblast Growth Factor 2 High-mobility Group Box 1 Ischaemia-reperfusion Acute Kidney Injury Mitochondrial Dysfunction Inflammatory Cytokine
刊名JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
2017-11-01
DOI10.1111/jcmm.13203
21期:11页:2909-2925
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]Cell Biology ; Research & Experimental Medicine
关键词[WOS]ISCHEMIA-REPERFUSION INJURY ; ACUTE KIDNEY INJURY ; CARDIAC-SPECIFIC OVEREXPRESSION ; SENSITIVE K+-CHANNEL ; DEPENDENT POTASSIUM CHANNEL ; OXIDATIVE STRESS ; REACTIVE OXYGEN ; NEPHROGENIC PROTEINS ; CEREBRAL-ISCHEMIA ; CELL APOPTOSIS
英文摘要Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and K-ATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K-ATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1 alpha, IL-6 and TNF alpha. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.
语种英语
WOS记录号WOS:000413962100024
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文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/149764
专题中国科学院大连化学物理研究所
作者单位1.Wenzhou Med Univ, Sch Pharmaceut Sci, Key Lab Biotechnol & Pharmaceut Engn, Wenzhou, Zhejiang, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Dept Biotechnol, Ctr Translat Med, Dalian, Liaoning, Peoples R China
3.Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Pediat Surg, Xian, Shaanxi, Peoples R China
4.Wenzhou Med Univ, Lab Anim Ctr, Wenzhou, Zhejiang, Peoples R China
5.Wenzhou Univ, Inst Life Sci, Wenzhou, Peoples R China
6.Justus Liebig Univ, Excellence Cluster Cardiopulm Syst, Giessen, Germany
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Tan, Xiao-Hua,Zheng, Xiao-Meng,Yu, Li-Xia,et al. Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2017,21(11):2909-2925.
APA Tan, Xiao-Hua.,Zheng, Xiao-Meng.,Yu, Li-Xia.,He, Jian.,Zhu, Hong-Mei.,...&Zhang, Jin-San.(2017).Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,21(11),2909-2925.
MLA Tan, Xiao-Hua,et al."Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 21.11(2017):2909-2925.
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