Yonsei Med J.  2020 Jan;61(1):85-93. 10.3349/ymj.2020.61.1.85.

Follistatin Mitigates Myofibroblast Differentiation and Collagen Synthesis of Fibroblasts from Scar Tissue around Injured Flexor Tendons

Affiliations
  • 1BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
  • 2Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea. YRCHOI@yuhs.ac

Abstract

PURPOSE
The aim of this study was to investigate the effect of FST gene on the inhibition of fibrosis in fibroblastic cells from scar tissue around repaired zone II flexor tendons.
MATERIALS AND METHODS
Immunohistochemistry was conducted on fibroblast cells transfected with adenovirus-LacZ (Ad-LacZ) as a marker gene (control), or with adenovirus-FST (Ad-FST) as a therapeutic gene. Fibroblast cultures without adenoviral exposure served as controls.
RESULTS
Fibroblastic cells transfected with Ad-FST demonstrated significant decrease in collagen type I, MMP-1, MMP2, and α-SMA mRNA expressions compared to those transfected with Ad-LacZ. In addition, fibroblastic cells transfected with Ad-FST exhibited significant decrease in MMP-1, TIMP-1, fibronectin, PAI-1, TRPV4, α-SMA, desmin, and PAX7 protein expressions.
CONCLUSION
Based on these findings, we conclude that FST may be a novel therapeutic strategy for preventing scar adhesions around repaired tendons by inhibiting fibroblasts from differentiating into myofibroblasts, in addition to producing type I collagen and regulating extracellular matrix turnover via the downregulation of MMP-1 and TIMP-1. FST may also decrease contracture of the scar by inhibiting Ca²âº-dependent cell contraction.

Keyword

Follistatin; tendon injuries; tendon adhesion; fibrosis; gene therapy

MeSH Terms

Cicatrix*
Collagen Type I
Collagen*
Contracture
Desmin
Down-Regulation
Extracellular Matrix
Fibroblasts*
Fibronectins
Fibrosis
Follistatin*
Genetic Therapy
Immunohistochemistry
Myofibroblasts*
Plasminogen Activator Inhibitor 1
RNA, Messenger
Tendon Injuries
Tendons*
Tissue Inhibitor of Metalloproteinase-1
Collagen
Collagen Type I
Desmin
Fibronectins
Follistatin
Plasminogen Activator Inhibitor 1
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-1
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