Qi Liu1, Liyang Chen1, Xuchun Liang1, Yuqing Cao1, Xinyue Zhu1, Siqi Wang1, Jin Li1, Juan Gao2, Junjie Xiao3. 1. Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China. 2. Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China. Electronic address: juangao@shu.edu.cn. 3. Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai 200444, China; Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai 200444, China. Electronic address: junjiexiao@shu.edu.cn.
Abstract
BACKGROUND: Exercise is beneficial for muscle atrophy. Peroxisome proliferator-activated receptor gamma (PPARγ) and microRNA-29b (miR-29b) have been reported to be responsible for angiotensin Ⅱ (AngⅡ)-induced muscle atrophy. However, it is unclear whether exercise can protect AngⅡ-induced muscle atrophy by targeting PPARγ/miR-29b. METHODS: Skeletal muscle atrophy in both the control group and the run group was established by AngⅡ infusion; after 1 week of exercise training, the mice were sacrificed, and muscle weight was determined. Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression level of muscle atrogenes, including F-box only protein 32 (FBXO32, also called Atrogin-1) and muscle-specific RING-finger 1 (MuRF-1), the phosphorylation level of protein kinase B (PKB, also called AKT)/forkhead box O3A (FOXO3A)/mammalian target of rapamycin (mTOR) pathway proteins, the expression level of PPARγ and apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteine-aspartic acid protease 3 (caspase-3), and cleaved-caspase-3, were determined by western blot. The expression level of miR-29b was checked by reverse-transcription quantitative polymerase chain reaction. A PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression was used to demonstrate whether PPARγ activation or miR-29b inhibition mediates the beneficial effects of exercise in AngⅡ-induced muscle atrophy. RESULTS: Exercise can significantly attenuate AngⅡ-induced muscle atrophy, which is demonstrated by increased skeletal muscle weight, cross-sectional area of myofiber, and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis. In AngⅡ-induced muscle atrophy mice models, PPARγ was elevated whereas miR-29b was decreased by exercise. The protective effects of exercise in AngⅡ-induced muscle atrophy were inhibited by a PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression. CONCLUSION: Exercise attenuates AngⅡ-induced muscle atrophy by activation of PPARγ and suppression of miR-29b.
BACKGROUND: Exercise is beneficial for muscle atrophy. Peroxisome proliferator-activated receptor gamma (PPARγ) and microRNA-29b (miR-29b) have been reported to be responsible for angiotensin Ⅱ (AngⅡ)-induced muscle atrophy. However, it is unclear whether exercise can protect AngⅡ-induced muscle atrophy by targeting PPARγ/miR-29b. METHODS: Skeletal muscle atrophy in both the control group and the run group was established by AngⅡ infusion; after 1 week of exercise training, the mice were sacrificed, and muscle weight was determined. Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression level of muscle atrogenes, including F-box only protein 32 (FBXO32, also called Atrogin-1) and muscle-specific RING-finger 1 (MuRF-1), the phosphorylation level of protein kinase B (PKB, also called AKT)/forkhead box O3A (FOXO3A)/mammalian target of rapamycin (mTOR) pathway proteins, the expression level of PPARγ and apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteine-aspartic acid protease 3 (caspase-3), and cleaved-caspase-3, were determined by western blot. The expression level of miR-29b was checked by reverse-transcription quantitative polymerase chain reaction. A PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression was used to demonstrate whether PPARγ activation or miR-29b inhibition mediates the beneficial effects of exercise in AngⅡ-induced muscle atrophy. RESULTS: Exercise can significantly attenuate AngⅡ-induced muscle atrophy, which is demonstrated by increased skeletal muscle weight, cross-sectional area of myofiber, and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis. In AngⅡ-induced muscle atrophymice models, PPARγ was elevated whereas miR-29b was decreased by exercise. The protective effects of exercise in AngⅡ-induced muscle atrophy were inhibited by a PPARγ inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression. CONCLUSION: Exercise attenuates AngⅡ-induced muscle atrophy by activation of PPARγ and suppression of miR-29b.