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PI3K/AKT/FOXO3a Pathway Induces Muscle Atrophy by Ubiquitin-Proteasome System and Autophagy System in COPD Rat Model

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Abstract

Muscle atrophy is a common extrapulmonary co-morbidity affecting about 20% of patients with COPD. However, the mechanism of muscle atrophy in COPD remains unclear. This study investigated the role of the ubiquitin-proteasome system (UPS) and the autophagy system in COPD muscle atrophy and its mechanism. A COPD rat model was established to evaluate the in vitro effects of the UPS and the autophagy system in muscle atrophy. In addition, the role of the UPS, autophagy systems, and the expressions of the PI3K/AKT/FOXO3a pathway were studied in the CSE-induced L6 myoblast cells. Furthermore, we evaluated the effect of FOXO3a in the CSE-induced L6 myoblast cells using siRNA-FOXO3a. The results showed that the expression of ubiquitin-related proteins and autophagy-related proteins were significantly increased in the COPD rat model and CSE-induced L6 myoblast cells. At the same time, there was a concurrent decrease in the phosphorylation protein expression of PI3K and AKT, but the transcriptional activity of FOXO3a was increased in CSE-induced L6 myoblast cells. And siRNA-FOXO3a significantly decreased the expression level of the UPS and the autophagy system in CSE-induced L6 myoblast cells. These results suggest that PI3K/AKT/FOXO3a participates in COPD muscle atrophy by regulating the UPS and the autophagy systems.

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No datasets were generated or analyzed during the current study.

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Funding

This research was supported by funds from Shanghai Natural Science Foundation (SNSF) Project (Contract grant number:14ZR1426800).

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  1. These authors contributed equally: Haiyang Yu, Guiyin Zhu

Authors and Affiliations

  1. Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Haiyang Yu, Guiyin Zhu, Dongmei Wang, Xuan Huang & Fengfeng Han

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Contributions

H.Y. and G.Z. contribute to the study conduct and draft the manuscript. D.W. and X.H. contribute to data analysis. F.H. contributes to the study design and guide. All authors reviewed the manuscript.

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Correspondence to Fengfeng Han.

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Yu, H., Zhu, G., Wang, D. et al. PI3K/AKT/FOXO3a Pathway Induces Muscle Atrophy by Ubiquitin-Proteasome System and Autophagy System in COPD Rat Model. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01232-w

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