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

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초록

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.

참고문헌 (38)

  1. Clayton RA, "The epidemiology of musculoskeletal tendinous and ligamentous injuries", Injury, 39, pp.1338~1344 (2008)
  2. Dy CJ, "The epidemiology of reoperation after flexor tendon repair", J Hand Surg Am, 37, pp.919~924 (2012)
  3. Dy CJ, "Complications after flexor tendon repair : a systematic review and metaanalysis", J Hand Surg Am, 37, pp.543~551 (2012)
  4. Hill C, "A regional audit of hand and wrist injuries. A study of 4873 injuries", J Hand Surg Br, 23, pp.196~200 (1998)
  5. Tang JB, "New developments are improving flexor tendon repair", Plast Reconstr Surg, 141, pp.1427~1437 (2018)
  6. Ketchum LD, "Effects of triamcinolone on tendon healing and function. A laboratory study", Plast Reconstr Surg, 47, pp.471~482 (1971)
  7. Kulick MI, "Injectable ibuprofen : preliminary evaluation of its ability to decrease peritendinous adhesions", Ann Plast Surg, 13, pp.459~467 (1984)
  8. Amiel D, "Hyaluronan in flexor tendon repair", J Hand Surg Am, 14, pp.837~843 (1989)
  9. Salti NI, "Effect of hyaluronic acid on rabbit profundus flexor tendon healing in vitro", J Surg Res, 55, pp.411~415 (1993)
  10. Wiig M, "Tendon repair--cellular activities in rabbit deep flexor tendons and surrounding synovial sheaths and the effects of hyaluronan : an experimental study in vivo and in vitro", J Hand Surg Am, 22, pp.818~825 (1997)
  11. Nyska M, "Decreased adhesion formation in flexor tendons by topical application of enriched collagen solution--a histological study", Arch Orthop Trauma Surg, 106, pp.192~194 (1987)
  12. Akali A, "Decrease in adhesion formation by a single application of 5-fluorouracil after flexor tendon injury", Plast Reconstr Surg, 103, pp.151~158 (1999)
  13. Karaaltin MV, "The effects of 5-fluorouracil on flexor tendon healing by using a biodegradable gelatin, slow releasing system : experimental study in a hen model", J Hand Surg Eur Vol, 38, pp.651~657 (2013)
  14. Bartle BK, "Development of a synthetic replacement for flexor tendon pulleys using expanded polytetrafluoroethylene membrane", Ann Plast Surg, 28, pp.266~270 (1992)
  15. Golash A, "Efficacy of ADCON-T", N after primary flexor tendon repair in Zone II : a controlled clinical trial, 2003, pp.28, 113~115
  16. Wynn TA, "Mechanisms of fibrosis : therapeutic translation for fibrotic disease", Nat Med, 18, pp.1028~1040 (2012)
  17. Chang J, "Studies in flexor tendon wound healing : neutralizing antibody to TGF-beta1 increases postoperative range of motion", Plast Reconstr Surg, 105, pp.148~155 (2000)
  18. Chen CH, "Effectiveness of microRNA in Down-regulation of TGF-beta gene expression in digital flexor tendons of chickens : in vitro and in vivo study", J Hand Surg Am, 34, pp.1777~1784 (2009)
  19. Bates SJ, "Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair", J Bone Joint Surg Am, 88, pp.2465~2472 (2006)
  20. Katzel EB, "Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing", J Orthop Res, 29, pp.684~693 (2011)
  21. Jørgensen HG, "Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon adhesion following transection", Cytokine, 30, pp.195~202 (2005)
  22. Lees VC, "A multicentre, randomized, double-blind trial of the safety and efficacy of mannose-6-phosphate in patients having Zone II flexor tendon repairs", J Hand Surg Eur Vol, 40, pp.682~694 (2015)
  23. Sugino K, "Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell", J Biol Chem, 268, pp.15579~15587 (1993)
  24. Hedger MP, "The regulation and functions of activin and follistatin in inflammation and immunity", Vitam Horm, 85, pp.255~297 (2011)
  25. Hashimoto O, "A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells. Endocytotic degradation of activin and its acceleration by follistatin associated with cell-surface heparan sulfate", J Biol Chem, 272, pp.13835~13842 (1997)
  26. Patella S, "Follistatin attenuates early liver fibrosis : effects on hepatic stellate cell activation and hepatocyte apoptosis", Am J Physiol Gastrointest Liver Physiol, 290, pp.G137~G144 (2006)
  27. Aoki F, "Attenuation of bleomycin-induced pulmonary fibrosis by follistatin", Am J Respir Crit Care Med, 172, pp.713~720 (2005)
  28. Forrester HB, "Identification of a radiation sensitivity gene expression profile in primary fibroblasts derived from patients who developed radiotherapy-induced fibrosis", Radiother Oncol, 111, pp.186~193 (2014)
  29. Koob TJ, "Tendon--bridging the gap", Comp Biochem Physiol A Mol Integr Physiol, 133, pp.905~909 (2002)
  30. Khanna A, "Prevention of adhesions in surgery of the flexor tendons of the hand : what is the evidence", Br Med Bull, 90, pp.85~109 (2009)
  31. Thomopoulos S, "Mechanisms of tendon injury and repair", J Orthop Res, 33, pp.832~839 (2015)
  32. Wu YF, "Adeno-associated virus-2-mediated TGF-β1 microRNA transfection inhibits adhesion formation after digital flexor tendon injury", Gene Ther, 23, pp.167~175 (2016)
  33. DePaolo LV, "Inhibins, activins, and follistatins : the saga continues", Proc Soc Exp Biol Med, 214, pp.328~339 (1997)
  34. Harrington AE, "Structural basis for the inhibition of activin signalling by follistatin", EMBO J, 25, pp.1035~1045 (2006)
  35. Moore CS, "An alternate perspective on the roles of TIMPs and MMPs in pathology", Am J Pathol, 180, pp.12~16 (2012)
  36. Hinz B, "Formation and function of the myofibroblast during tissue repair", J Invest Dermatol, 127, pp.526~537 (2007)
  37. Sandbo N, "Actin cytoskeleton in myofibroblast differentiation : ultrastructure defining form and driving function", Transl Res, 158, pp.181~196 (2011)
  38. Follonier Castella L, "Regulation of myofibroblast activities : calcium pulls some strings behind the scene", Exp Cell Res, 316, pp.2390~2401 (2010)

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