1. Academic Validation
  2. Exercise Attenuate Diaphragm Atrophy in COPD Mice via Inhibiting the RhoA/ROCK Signaling

Exercise Attenuate Diaphragm Atrophy in COPD Mice via Inhibiting the RhoA/ROCK Signaling

  • Int J Chron Obstruct Pulmon Dis. 2024 Jul 8:19:1591-1601. doi: 10.2147/COPD.S460182.
Peijun Li # 1 Yingqi Wang # 1 Yuanyuan Cao 2 Jiacheng Shi 1 Meiling Jiang 2 Xiaoyu Han 2 Linhong Jiang 1 Yidie Bao 1 Weibing Wu 2 Xiaodan Liu 1 3 4
Affiliations

Affiliations

  • 1 School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
  • 2 Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People's Republic of China.
  • 3 Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
  • 4 Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People's Republic of China.
  • # Contributed equally.
Abstract

Background: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.

Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.

Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.

Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.

Keywords

RhoA/ROCK signaling; chronic obstructive pulmonary disease; diaphragmatic atrophy; exercise training; inflammation.

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