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The Role of Activin B in Skeletal Muscle Injury and Regeneration

Activin B, a member of the transforming growth factor-β superfamily, is ubiquitously expressed in diverse tissues and is a regulator of reproduction, embryonic development, and adult tissue homeostasis. We aimed to determine whether activin B is involved in skeletal muscle injury and if selective inhibition of activin B would provide a regenerative benefit. The local introduction of activin B into normal skeletal muscle increased the expression of inflammatory and muscle atrophy genes TWEAK, TNFα, GDF3 and TRIM63, by 2-, 10-, 10-, and 4-fold, respectively. The data indicate a sensitive response of skeletal muscle to activin B. Six hours after cardiotoxin-induced skeletal muscle damage, circulating activin B protein expression in serum increased by 9-fold and InhβB gene expression increased by 30-fold in muscle. After cardiotoxin-induced skeletal muscle damage, activin B protein expression in muscle was significantly increased at 48- and 120-hours by 1.5 and 2-fold, respectively. Muscle histopathological features showed that activin B antibody–treated mice displayed a reduction in necrotic debris, with a concomitant reduction in intramyocellular space at 9-days after injury. Activin B treated C2C12 myoblasts also displayed a dose-dependent reduction in active myogenesis. Furthermore, the increased presence of activin B early in muscle injury impedes muscle repair and remodeling. In summary, acute muscle injury leads to increases in activin B levels and when selectively neutralized with a monoclonal antibody, there is augmented skeletal muscle repair.

  1. 10.25394/pgs.17131340.v1
Identiferoai:union.ndltd.org:purdue.edu/oai:figshare.com:article/17131340
Date20 December 2021
CreatorsMelissa A Yaden (11798105)
Source SetsPurdue University
Detected LanguageEnglish
TypeText, Thesis
RightsCC BY 4.0
Relationhttps://figshare.com/articles/thesis/The_Role_of_Activin_B_in_Skeletal_Muscle_Injury_and_Regeneration/17131340

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