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Preconditioning of cardiac stem cells by electrical stimulation induces cytoprotection against oxidative stress through release of connective tissue growth factor by miR‐378 downregulation
Author(s) -
Kim Sun Wook,
Kim Ha Won,
Huang Wei,
Wang Yigang,
Ashraf Muhammad
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1217.31
Subject(s) - ctgf , cytoprotection , stem cell , protein kinase b , growth factor , microbiology and biotechnology , pi3k/akt/mtor pathway , chemistry , biology , oxidative stress , cancer research , signal transduction , endocrinology , biochemistry , receptor
Survival of stem cells following transplantation in the infarcted myocardium is a critical issue for the cell‐based therapy and preconditioning (PC) of stem cells is a method for cytoprotection. In this study, we investigated the cytoprotective effect of PC with electrical stimulation (EleS) on cardiac stem cells (CSCs) survival. Sca‐1 + CSCs were isolated from male C57BL6 mice hearts. PC of CSCs with EleS ( EleS CSCs) was carried out for 3 h at 1.5 V followed by exposure to H 2 O 2 . Cytoprotective effects and cell adhesion ability were significantly increased by EleS as evaluated by TUNEL, lactate dehyrogenase release assay and adhesion assay as well as Sry gene analysis in vivo . EleS increased phosphorylation of AKT, FAK and GSK3β, and decreased pro‐apoptotic protein caspase‐3 cleavage. Pretreatment with Wortmannin, a PI3K inhibitor, and FAK inhibitor‐14 abolished the pro‐survival effects of EleS. Importantly, we found that connective tissue growth factor ( Ctgf ) is a key determinant for EleS‐induced CSC survival and adhesion. Furthermore, we identified miR‐378 is a potential negative regulator for Ctgf expression in EleS CSCs. In conclusion, EleS enhanced CSC survival in vitro and in vivo through AKT/FAK/CTGF/miR‐378 signaling cascade, being suggested as a novel preconditioining strategy. This work was supported by National Institutes of Health grant, [HL087246 to M.A.].