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Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis

Zhu, J and Li, Y and Lu, A and Gharaibeh, B and Ma, J and Kobayashi, T and Quintero, AJ and Huard, J (2011) Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis. American Journal of Pathology, 179 (2). 915 - 930. ISSN 0002-9440

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Recovery from skeletal muscle injury is often incomplete because of the formation of fibrosis and inadequate myofiber regeneration; therefore, injured muscle could benefit significantly from therapies that both stimulate muscle regeneration and inhibit fibrosis. To this end, we focused on blocking myostatin, a member of the transforming growth factorβ superfamily and a negative regulator of muscle regeneration, with the myostatin antagonist follistatin. In vivo, follistatin-overexpressing transgenic mice underwent significantly greater myofiber regeneration and had less fibrosis formation compared with wild-type mice after skeletal muscle injury. Follistatin's mode of action is likely due to its ability to block myostatin and enhance neovacularization. Furthermore, muscle progenitor cells isolated from follistatin-overexpressing mice were significantly superior to muscle progenitors isolated from wild-type mice at regenerating dystrophin-positive myofibers when transplanted into the skeletal muscle of dystrophic mdx/severe combined immunodeficiency mice. In vitro, follistatin stimulated myoblasts to express MyoD, Myf5, and myogenin, which are myogenic transcription factors that promote myogenic differentiation. Moreover, follistatin's ability to enhance muscle differentiation is at least partially due to its ability to block myostatin, activin A, and transforming growth factorβ1, all of which are negative regulators of muscle cell differentiation. The findings of this study suggest that follistatin is a promising agent for improving skeletal muscle healing after injury and muscle diseases, such as the muscular dystrophies. © 2011 American Society for Investigative Pathology.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhu, J
Li, Y
Lu, A
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Ma, J
Kobayashi, T
Quintero, AJ
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 August 2011
Date Type: Publication
Journal or Publication Title: American Journal of Pathology
Volume: 179
Number: 2
Page Range: 915 - 930
DOI or Unique Handle: 10.1016/j.ajpath.2011.04.008
Schools and Programs: School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0002-9440
MeSH Headings: Animals; Cell Line; Cell Transplantation; Fibrosis--pathology; Follistatin--chemistry; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence--methods; Muscle, Skeletal--metabolism; MyoD Protein--metabolism; Myogenic Regulatory Factor 5--metabolism; Myostatin--metabolism; Neovascularization, Pathologic; Regeneration; Transforming Growth Factor beta--metabolism
Other ID: NLM PMC3157209
PubMed Central ID: PMC3157209
PubMed ID: 21689628
Date Deposited: 04 Apr 2014 16:37
Last Modified: 02 May 2018 12:55


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