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Circulating miR‐122‐5p: A Novel Exerkine in Exercise‐induced Angiogenesis
Author(s) -
Wu Jie,
Hou Zuoxu,
Li Guohua,
Zhang Xing,
Gao Feng
Publication year - 2019
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.2019.33.1_supplement.536.1
Subject(s) - angiogenesis , cd31 , cd36 , endocrinology , medicine , chemistry , neovascularization , transfection , mapk/erk pathway , biology , kinase , biochemistry , receptor , gene
Physical exercise effectively boosts angiogenesis in skeletal muscles, but the mechanisms remain poorly understood. Our previous study showed that 4‐week swimming training (1.5 h×2/d, 7 d/wk×4 weeks) significantly promoted angiogenesis in skeletal muscle. And we had found the expression of several circulating miRNAs profoundly changed. Among which, miR‐122‐5p, a liver specific microRNA, promoted endothelial proliferation significantly. Here we further determined the role of circulating miR‐122‐5p in exercise‐induced angiogenesis. Exercised mice (running wheel training, 1.5 h/d ×9 d) exhibited elevated miR‐122‐5p in serum and aorta (2.132±0.294, 3.275±0.819 fold of Sedentary, p<0.05), concomitant with increased capillary density in the quadriceps marked with fluorescent CD31 (3.562±0.354 fold of Sedentary, p<0.01). Whereas, tail vein injection of miR‐122‐5p antagomir partially decreased the exercise‐induced VEGF expression and CD31 staining in quadriceps, suggesting that elevated circulating mir‐122‐5p partially contributes to the exercise‐induced angiogenesis. In vitro study on primary aortic endothelial cells (ECs) transfected with miR‐122‐5p mimic showed increased tube numbers, migration distance and relative sprouting distance, accompanied with increased expression of p‐ERK/ERK and VEGF. Mechanistically, miR‐122‐5p mimic increased the expression of CD36, CPT1a and CPT1b together with the uptake of fatty acid assessed by BODIPY fluorescence intensity in ECs, suggesting an increased free fatty acid (FFA) metabolism. Transfection of CD36 siRNA blunted the pro‐angiogenic effect of miR‐122‐5p. In conclusion, our findings demonstrate that exercise‐induced proangiogenic effects are partly attributed to elevated circulating miR‐122‐5p via increasing endothelial FFA metabolism. Support or Funding Information This study was supported by the grants from the National Natural Science Foundation of China (Grant No. 816770253) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .