Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation

doi:10.1371/journal.pone.0082275

科研成果详情

题名	Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation
作者	Zhang, Chi 1,2; Shao, Minglong1,2,3; Yang, Hong2; Chen, Liangmiao2; Yu, Lechu1,2; Cong, Weitao1,3; Tian, Haishan3; Zhang, Fangfang 1,2; Cheng, Peng 1,2; Jin, Litai1,3; Tan, Yi1,2,4; Li, Xiaokun1,3; Cai, Lu1,2,4; Lu, Xuemian1,2
发表日期	2013-12-09
发表期刊	PLOS ONE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	ACTIVATED PROTEIN-KINASE ; CHRONIC KIDNEY-DISEASE ; OXIDATIVE STRESS ; FATTY-ACIDS ; LIPID NEPHROTOXICITY ; METABOLIC SYNDROME ; SODIUM RETENTION ; DB/DB MICE ; KAPPA-B ; NEPHROPATHY
摘要	Background: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia). Increasing evidence suggests that fibroblast growth factor (FGF) 21 has a crucial role in lipid metabolism under diabetic conditions. Objective: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. Methods: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight) or streptozotocin (150 mg/kg) to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 mu g/kg) for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. Results: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. Conclusion: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.
资助项目	National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81370917, 81000294]; Wenzhou Medical University [QTJ13005]; China-Canada Joint Health Research Initiative [81061120517]; Starting-Up Fund for Chinese-American Research Institute for Diabetic Complications from Wenzhou Medical University
出版者	PUBLIC LIBRARY SCIENCE
出版地	SAN FRANCISCO
ISSN	1932-6203
卷号	8 期号:12 页码:e82275.
DOI	10.1371/journal.pone.0082275
页数	11
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000328705200069
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	24349242
PMC记录号	PMC3857822
SCOPUSEID	2-s2.0-84891947508
通讯作者地址	[Cai, Lu]Chinese-American Research Institute for Diabetic Complications,Wenzhou Medical University,China
Scopus学科分类	Multidisciplinary
引用统计	被引频次：59[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/4308
专题	温州医科大学药学院（分析测试中心）其他_附属第三医院（瑞安市人民医院）
通讯作者	Cai, Lu
作者单位	1.Chinese-American Research Institute for Diabetic Complications,Wenzhou Medical University,China; 2.Ruian Center of the Chinese-American Research Institute for Diabetic Complications,Third Affiliated Hospital,Wenzhou Medical University,China; 3.School of Pharmacy,Wenzhou Medical University,China; 4.Kosair Children's Hospital Research Institute,Department of Pediatrics,University of Louisville,United States
第一作者单位	温州医科大学; 其他_附属第三医院（瑞安市人民医院）
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Zhang, Chi,Shao, Minglong,Yang, Hong,et al. Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation[J]. PLOS ONE,2013,8(12):e82275..
APA	Zhang, Chi., Shao, Minglong., Yang, Hong., Chen, Liangmiao., Yu, Lechu., ... & Lu, Xuemian. (2013). Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation. PLOS ONE, 8(12), e82275..
MLA	Zhang, Chi,et al."Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation".PLOS ONE 8.12(2013):e82275..