Roles of TGF-β/Smad signaling pathway in pathogenesis and development of gluteal muscle contracture

Abstract

Purpose of the study: Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles which is characterized by excessive deposition of collagen in the extracellular matrix. Transforming growth factor (TGF)-βs have been shown to play an important role in the progression of GMC. However, the underlying mechanisms are not entirely clear. We sought to explore the expression of TGF-β/Smad pathway proteins and their downstream targets in gluteal muscle contracture disease.

Materials and methods: The expression levels of collagens type I/III, TGF-β1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured using immunohistochemistry, reverse transcription and polymerase chain reaction (RT-PCR) and western blot assays.

Results: The expressions of collagens type I/III and TGF-β1 were significantly increased in the contraction band compared with unaffected muscle. In addition, R-Smad phosphorylation and Smad4 protein expression in the contraction band were also elevated, while the expression of Smad7 was significantly decreased in the fibrotic muscle of the GMC patients compared to the unaffected adjacent muscle. The protein and mRNA levels of PAI-1 were also remarkably increased in the contraction band compared with adjacent muscle. Immunohistochemical analysis also demonstrated that the expression levels of TGF-β1 and PAI-1 were higher in contraction band than those in the adjacent muscle.

Conclusion: Our data confirm the stimulating effects of the TGF-β/Smad pathway in gluteal muscle contracture disease and reveal the internal changes of TGF-β/Smad pathway proteins and their corresponding targets in gluteal muscle contracture patients.

• Gluteal muscle contracture
• PAI-1
• Smad2/3
• Smad7
• TGF-β/Smad pathway

Acknowledgments

We thank Mr XiaoPeng Tian for technical assistance and Mrs XiaoMin Yin from the Department of Pathology of Peking University Shen Zhen Hospital for providing and processing samples. XTZ and WTZ are the lead investigators and developed the design of the study, carried out data-acquisition, analysis, interpretations, and prepared the manuscript as primary authors. TY, HL and QZ assisted in carrying out data acquisition and were involved in preparing the study design. All authors read, edited, and approved the final manuscript.

Declaration of interest

The authors declare that they have no competing interests.