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Overexpression of nutrient sensor, AMP activated kinase (AMPK), in skeletal muscle enhances muscle stem cell transplantation efficiency
Author(s) -
Kang Gyumin,
Lee Dylan,
Liu Eden,
Jang Young Charles
Publication year - 2016
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.30.1_supplement.1245.19
Subject(s) - ampk , transplantation , skeletal muscle , amp activated protein kinase , stem cell , protein kinase a , cancer research , medicine , endocrinology , microbiology and biotechnology , biology , kinase
Calorie restriction (CR) is a robust dietary intervention that extends lifespan and delays, prevents, or reduces the severity of age‐related pathologies in variety of species. Previously, we have shown that CR significantly improves muscle stem cell (MuSC) function and enhances muscle stem cell transplantation efficiency. Similarly, when 8‐week treadmill endurance exercise training protocol was implemented to the mice, we found that MuSC content was significantly elevated and showed improvement in regenerative potential, as well as engraftment of MuSC. Thus, we hypothesized that the AMP activated kinase (AMPK), nutrient sensing protein and a common pathway activated by both CR and exercise, is responsible for this improvement in muscle stem cell function. In order to test the role of AMPK in MuSC function, we overexpressed a constitutively active AMPK or control vector in the recipient muscles 2 weeks prior to MuSC transplantation by in vivo electroporation. In concert with the CR and exercise, upregulation of AMPK significantly enhanced MuSC content and elevated MuSC engraftment efficiency compared to the control. These data indicate that metabolic reprograming by AMPK mimics CR and exercise effect, and may play a critical role in regulating stem cell niche, suggesting a simple means to improve the targeting and transplant of MuSC for potential therapy in muscle disorders.