title: miR-628 Promotes Burn-Induced Skeletal Muscle Atrophy via Targeting IRS1.
abstract: Skeletal muscle atrophy is a common clinical feature among patients with severe burns. Previous studies have shown that miRNAs play critical roles in the regulation of stress-induced skeletal muscle atrophy. Our previous study showed that burn-induced skeletal muscle atrophy is mediated by miR-628. In this study, compared with sham rats, rats subjected to burn injury exhibited skeletal muscle atrophy, as well as significantly decreased insulin receptor substrate 1 (IRS1) protein expression and significantly increased skeletal muscle cell apoptosis. An miRNA array showed that the levels of miR-628, a potential regulator of IRS1 protein translation, were also clearly elevated. Second, L6 myocyte cell apoptosis increased after induction of miR-628 expression, and IRS1 and p-Akt protein expression decreased significantly. Expression of the cell apoptosis-related proteins FoxO3a and cleaved caspase 3 also increased after induction of miR-628 expression. Finally, forced miR-628 expression in normal rats resulted in increased cell apoptosis and skeletal muscle atrophy, as well as changes in IRS1/Akt/FoxO3a signaling pathway activity consistent with the changes in protein expression described above. Inhibiting cell apoptosis with Z-VAD-FMK resulted in alleviation of burn-induced skeletal muscle atrophy. In general, our results indicate that miR-628 mediates burn-induced skeletal muscle atrophy by regulating the IRS1/Akt/FoxO3a signaling pathway.
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Jiake
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Haijun
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Wanli
authors.initials: W
authors.lastname: Chu
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Huinan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Burn & Plastic Surgery, the First Affiliated Hospital of PLA General Hospital, Beijing, 100048 China.
authors.forename: Mengjing
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs
keywords: Burn; IRS1; Skeletal muscle atrophy.; miR-628