https://orcid.org/0000-0003-4548-2309
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
Purpose
The two structural components contributing to joint contracture formation are myogenic and arthrogenic contracture, and myofibrosis is an important part of myogenic contracture. Myofibrosis is a response to long-time immobilization and is described as a condition with excessive deposition of endomysial and perimysial connective tissue components in skeletal muscle. The purpose of this study was to confirm whether metformin can attenuate the formation of myogenic contracture and myofibrosis through the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and inhabitation of subsequent transforming growth factor beta (TGF-β) 1/Smad signaling pathway.
Materials and Methods
An immobilized rat model was used to determine whether metformin could inhibit myogenic contracture and myofibrosis. The contents of myogenic contracture of knee joint was calculated by measuring instrument of range of motion (ROM), and myofibrosis of rectus femoris were determined by ultrasound shear wave elastography and Masson staining. Protein expression of AMPK and subsequent TGF-β1/Smad signaling pathway were determined by western blot. Subsequently, Compound C, a specific AMPK inhibitor, was used to further clarify the role of the AMPK-mediated inhibition of TGF-β1/Smad signaling pathway.
Results
We revealed that the levels of myogenic contracture and myofibrosis were gradually increased during immobilization, and overexpression of TGF-β1-induced formation of myofibrosis by activating Smad2/3 phosphorylation. Activation of AMPK by metformin suppressed overexpression of TGF-β1 and TGF-β1-induced Smad2/3 phosphorylation, further reducing myogenic contracture and myofibrosis during immobilization. In contrast, inhibition of AMPK by Compound C partially counteracted the inhibitory effect of TGF-β1/Smad signaling pathway by metformin.
Conclusion
Notably, we first illustrated the therapeutic effect of metformin through AMPK-mediated inhibition of TGF-β1/Smad signaling pathway in myofibrosis, which may provide a new therapeutic strategy for myogenic contracture.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Availability of data and material
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. All data generated or analyzed during this study are included in this published article. The manuscript, including related data, figures, and tables have not been previously published and are not under consideration elsewhere.
Authors’ contributions
Feng Wang conceived of the study, and participated in its design and coordination and drafted the manuscript. Chen Xu Zhou carried out the animal experiments and the molecular studies. Zhi Zheng performed the ultrasound shear wave elastography in the revised manuscript. Du Juan Li and Wen Li performed the statistical analysis. Yun Zhou conceived of the supplementary study, and participated in its design and coordination. All authors read and approved the final manuscript.
Ethics approval and consent to participate
The experimental procedures and the animal use and care protocols were approved by the Institutional Animal Care and Use Committee of Wannan Medical College (WNMC20200116).