title: bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway.
abstract: Autophagy is involved in the development and/or progression of many diseases, including myocardial ischemia/reperfusion (I/R). In this study, we hypothesized a protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the myocardial I/R model. Our results showed that bFGF improved heart function recovery and increased the survival of cardiomyocytes in myocardial I/R model. The protective effect of bFGF is related to the inhibition of LC3II levels. Additionally, bFGF enhances the clearance of Ub by p62 and increases the survival of H9C2 cells. Moreover, silencing of p62 partially blocks the clearance of Ub and abolishes the anti-apoptosis effect of bFGF. An shRNA against the autophagic machinery Atg7 increased the survival of H9C2 cells co-treated with bFGF and rapamycin. bFGF activates the downstream signaling of the PI3K/Akt/mTOR pathway. These results indicate that the role of bFGF in myocardial I/R recovery is related to the inhibition of excessive autophagy and increased ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new direction for bFGF drug development for heart disease and identifies protein signaling pathways involved in bFGF action.
authors: 1] School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China [2] Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China.
authors: Zhou-Guang
authors: ZG
authors: Wang
authors: 1] School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China [2] Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China.
authors: Yue
authors: Y
authors: Wang
authors: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors: Yan
authors: Y
authors: Huang
authors: Department of Pediatric Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.
authors: Qin
authors: Q
authors: Lu
authors: Department of Ultrasound, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.
authors: Lei
authors: L
authors: Zheng
authors: Department of Medical Immunology, Medical School, Anhui University of Science and Technology, Huainan 232001, China.
authors: Dong
authors: D
authors: Hu
authors: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors: Wen-Ke
authors: WK
authors: Feng
authors: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors: Yan-Long
authors: YL
authors: Liu
authors: Department of Pediatric Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.
authors: Kang-Ting
authors: KT
authors: Ji
authors: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors: Hong-Yu
authors: HY
authors: Zhang
authors: Institute of Basic Medical Science, Chinese PLA General Hospital, Beijing 100853, China.
authors: Xiao-Bing
authors: XB
authors: Fu
authors: 1] School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China [2] Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China.
authors: Xiao-Kun
authors: XK
authors: Li
authors: Department of Pediatric Cardiology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000, China.
authors: Mao-Ping
authors: MP
authors: Chu
authors: School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors: Jian
authors: J
authors: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005355:Fibrosis; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism*
chemical_list: D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D057149:Ubiquitinated Proteins