Follistatin Mitigates Myofibroblast Differentiation and Collagen Synthesis of Fibroblasts from Scar Tissue around Injured Flexor Tendons
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Purpose: The aim of this study was to investigate the effect of FST gene on the inhibition of fibrosis in fibroblastic cells from scartissue 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 exposureserved as controls. Results: Fibroblastic cells transfected with Ad-FST demonstrated significant decrease in collagen type I, MMP-1, MMP2, andα-SMA mRNA expressions compared to those transfected with Ad-LacZ. In addition, fibroblastic cells transfected with Ad-FSTexhibited 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 adhesionsaround repaired tendons by inhibiting fibroblasts from differentiating into myofibroblasts, in addition to producing type I collagenand regulating extracellular matrix turnover via the downregulation of MMP-1 and TIMP-1. FST may also decrease contractureof the scar by inhibiting Ca2+-dependent cell contraction.
Abstract
Purpose: The aim of this study was to investigate the effect of FST gene on the inhibition of fibrosis in fibroblastic cells from scartissue 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 exposureserved as controls. Results: Fibroblastic cells transfected with Ad-FST demonstrated significant decrease in collagen type I, MMP-1, MMP2, andα-SMA mRNA expressions compared to those transfected with Ad-LacZ. In addition, fibroblastic cells transfected with Ad-FSTexhibited 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 adhesionsaround repaired tendons by inhibiting fibroblasts from differentiating into myofibroblasts, in addition to producing type I collagenand regulating extracellular matrix turnover via the downregulation of MMP-1 and TIMP-1. FST may also decrease contractureof the scar by inhibiting Ca2+-dependent cell contraction.
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