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Int J Sports Med 2013; 34(09): 789-794
DOI: 10.1055/s-0032-1333284
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

The Fibrotic Role of Phosphatidylinositol-3-kinase/Akt Pathway in Injured Skeletal Muscle after Acute Contusion

H.-Y. Li
1   Department of Sports Medicine, Huashan Hospital, Sports Medicine Center of Fudan University, Shanghai, China
,
Q.-G. Zhang
2   Department of orthopaedics, Taizhou Hospital, Taizhou, Zhejiang, China
,
J.-W. Chen
1   Department of Sports Medicine, Huashan Hospital, Sports Medicine Center of Fudan University, Shanghai, China
,
S.-Q. Chen
1   Department of Sports Medicine, Huashan Hospital, Sports Medicine Center of Fudan University, Shanghai, China
,
S.-Y. Chen
1   Department of Sports Medicine, Huashan Hospital, Sports Medicine Center of Fudan University, Shanghai, China
› Author Affiliations
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Publication History



accepted after revision 18 December 2012

Publication Date:
26 February 2013 (online)

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Abstract

Transforming growth factor β (TGF-β) is a multifunctional cytokine with fibrogenic properties. Previous studies demonstrated that Phosphatidylinositol 3-Kinase (PI3K)/Akt/ mammalian target of Ramycin (mTOR), a non-Smad TGF-β pathway, plays an important role in the fibrotic pathogenesis of different organs such as the lung, kidney, skin and liver. However, the role of PI3k-Akt pathway in fibrosis in injured skeletal muscle is still unclear. In this study, we determined the fibrotic role of PI3K-Akt pathway in injured skeletal muscle. We established a mouse model for acute muscle contusion. Western blotting analysis showed that TGF-β, phosphorylated Akt and phosphorylated mTOR were increased in muscles after acute contusion, which indicated that the PI3K-Akt- mTOR pathway was activated in skeletal muscle after acute contusion. The pathway was inhibited by a PI3K inhibitor, LY294002. Moreover, the expression of fibrosis markers vimentin, α SMA and collagen I and the area of scar decreased in injured skeletal muscle after PI3K pathway was blocked. The muscle function improved in terms of both fast-twitch and tetanic strength after PI3K/Akt pathway was inhibited in injured skeletal muscle. In conclusion, activation of PI3K-Akt-mTOR pathway might promote collagen production and scar formation in the acute contused skeletal muscle. Blocking of PI3K-Akt-mTOR pathway could improve the function of injured skeletal muscle.

Key words

Fibrosis - muscle injuries - phosphatidylinositol-3-kinase - akt - mammalian target of ­Ramycin
 

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