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Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy.
Cheng, Yanli; Zhang, Jingjing; Guo, Weiying; Li, Fengsheng; Sun, Weixia; Chen, Jing; Zhang, Chi; Lu, Xuemian; Tan, Yi; Feng, Wenke; Fu, Yaowen; Liu, Gilbert C; Xu, Zhonggao; Cai, Lu.
Afiliação
  • Cheng Y; The First Hospital of Jilin University, Changchun 130021, China; The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou 325035, China; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40
  • Zhang J; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA; Department of Cardiology at the First Hospital of China Medical University, Shenyang 110016, China; Department of Cardiology at the People's Hospital of Liaoning Province, Sh
  • Guo W; The First Hospital of Jilin University, Changchun 130021, China.
  • Li F; The Second Artillery General Hospital, Beijing 100088, China.
  • Sun W; The First Hospital of Jilin University, Changchun 130021, China.
  • Chen J; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
  • Zhang C; The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou 325035, China; The Third Affiliated Hospital of the Wenzhou Medical University, Ruian 325200, China.
  • Lu X; The Third Affiliated Hospital of the Wenzhou Medical University, Ruian 325200, China.
  • Tan Y; The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou 325035, China; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA; The Third Affiliated Hospital of the Wenzhou Medical Un
  • Feng W; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA; Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
  • Fu Y; The First Hospital of Jilin University, Changchun 130021, China.
  • Liu GC; Child and Adolescent Health Research Design and Support, University of Louisville, Louisville, KY 40204, USA.
  • Xu Z; The First Hospital of Jilin University, Changchun 130021, China. Electronic address: renalxu@163.com.
  • Cai L; The Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou 325035, China; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA; The Third Affiliated Hospital of the Wenzhou Medical Un
Free Radic Biol Med ; 93: 94-109, 2016 Apr.
Article em En | MEDLINE | ID: mdl-26849944
ABSTRACT
The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3ß phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. All these adverse effects were significantly attenuated by FF treatment. FF also significantly increased fibroblast growth factor 21 (FGF21) expression and enhanced Nrf2 function in diabetic and non-diabetic kidneys. Moreover, FF-induced amelioration of diabetic renal damage, including the stimulation of PI3K/Akt/GSK-3ß/Fyn pathway and the enhancement of Nrf2 function were abolished in FGF21-null mice, confirming the critical role of FGF21 in FF-induced renal protection. These results suggest for the first time that FF prevents the development of DN via up-regulating FGF21 and stimulating PI3K/Akt/GSK-3ß/Fyn-mediated activation of the Nrf2 pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenofibrato / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Fator 2 Relacionado a NF-E2 / Fatores de Crescimento de Fibroblastos Limite: Animals / Humans Idioma: En Revista: Free Radic Biol Med Assunto da revista: BIOQUIMICA / MEDICINA Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenofibrato / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Fator 2 Relacionado a NF-E2 / Fatores de Crescimento de Fibroblastos Limite: Animals / Humans Idioma: En Revista: Free Radic Biol Med Assunto da revista: BIOQUIMICA / MEDICINA Ano de publicação: 2016 Tipo de documento: Article