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HGF suppresses the production of collagen type III and α-SMA induced by TGF-β1 in healing fibroblasts

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Abstract

The aim of this study was to examine the effectiveness of HGF in blocking TGF-β1-induced collagen III and α-smooth muscle actin (α-SMA) production in rat healing fibroblasts, fibroblasts were obtained from healing medial collateral ligament (MCL) injury. Cell culture was supplemented with 5 ng/ml of TGF-β1 along with increasing doses of HGF (10–40 ng/ml). The productions of collagen III in supernatants culture were assayed by enzyme-linked immunosorbent assay. Expression of α-SMA was assessed by Western blot. Treatment with TGF-β1 significantly stimulated collagen III and α-SMA production in healing fibroblasts. Remarkably, the addition of HGF reduced productions of all components induced by TGF-β1 in a dose-dependent manner. This study shows that HGF antagonizes the action of TGF-β1 effectively in cultured healing MCL injury fibroblasts. The results provide a cellular and molecular basis for HGF’s acting as a therapeutic agent for MCL scar formation and poor healing.

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References

  • Agarwal C, Britton ZT, Alaseirlis DA, Li Y, Wang JH (2006) Healing and normal fibroblasts exhibit differential proliferation, collagen production, alpha-SMA expression, and contraction. Ann Biomed Eng 34(4):653–659

    Article  PubMed  Google Scholar 

  • Anitua E, Sanchez M, Nurden AT, Zalduendo M, de la Fuente M, Azofra J, Andia I (2007) Reciprocal actions of platelet-secreted TGF-beta1 on the production of VEGF and HGF by human tendon cells. Plast Reconstr Surg 119(3):950–959

    Article  PubMed  CAS  Google Scholar 

  • Brzozowski T, Konturek PC, Konturek SJ, Schuppan D, Drozdowicz D, Kwiecień S, Majka J, Nakamura T, Hahn E (2001) Effect of local application of growth factors on gastric ulcer healing and mucosal expression of cyclooxygenase-1 and -2. Digestion 64(1):15–29

    Article  PubMed  CAS  Google Scholar 

  • Chang J, Thunder R, Most D, Longaker MT, Lineaweaver WC (2000) Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion. Plast Reconstr Surg 105(1):148–155

    Article  PubMed  CAS  Google Scholar 

  • Conway K, Price P, Harding KG, Jiang WG (2006) The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing. Wound Repair Regen 14(1):2–10

    Article  PubMed  Google Scholar 

  • Dahlgren LA, Mohammed HO, Nixon AJ (2005) Temporal expression of growth factors and matrix molecules in healing tendon lesions. J Orthop Res 23(1):84–92

    Article  PubMed  CAS  Google Scholar 

  • Dai C, Liu Y (2004) Hepatocyte growth factor antagonizes the profibrotic action of TGF-beta1 in mesangial cells by stabilizing Smad transcriptional corepressor TGIF. J Am Soc Nephrol 15(6):1402–1412

    Article  PubMed  CAS  Google Scholar 

  • Eriksen HA, Pajala A, Leppilahti J, Risteli J (2002) Increased content of type III collagen at the rupture site of human Achilles tendon. J Orthop Res 20(6):1352–1357

    Article  PubMed  CAS  Google Scholar 

  • Frank C, Woo SL, Amiel D, Harwood F, Gomez M, Akeson W (1983) Medial collateral ligament healing. A multidisciplinary assessment in rabbits. Am J Sports Med 11(6):379–389

    Article  PubMed  CAS  Google Scholar 

  • Fu SC, Wong YP, Cheuk YC, Lee KM, Chan KM (2005) TGF-beta1 reverses the effects of matrix anchorage on the gene expression of decorin and procollagen type I in tendon fibroblasts. Clin Orthop Relat Res 431:226–232

    Article  PubMed  Google Scholar 

  • Hirano S, Bless D, Heisey D, Ford C (2003) Roles of hepatocyte growth factor and transforming growth factor beta1 in production of extracellular matrix by canine vocal fold fibroblasts. Laryngoscope 113(1):144–148

    Article  PubMed  CAS  Google Scholar 

  • Klein MB, Yalamanchi N, Pham H, Longaker MT, Chang J (2002) Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production. J Hand Surg Am 27(4):615–620

    Article  PubMed  Google Scholar 

  • Molloy T, Wang Y, Murrell G (2003) The roles of growth factors in tendon and ligament healing. Sports Med 33(5):381–394

    Article  PubMed  Google Scholar 

  • Nakamura T, Sakata R, Ueno T, Sata M, Ueno H (2000) Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine- treated rats. Hepatology 32(2):247–255

    Article  PubMed  CAS  Google Scholar 

  • Nakamura T, Matsumoto K, Mizuno S, Sawa Y, Matsuda H, Nakamura T (2005) Hepatocyte growth factor prevents tissue fibrosis, remodeling, and dysfunction in cardiomyopathic hamster hearts. Am J Physiol Heart Circ Physiol 288(5):H2131–H2139

    Article  PubMed  CAS  Google Scholar 

  • Natsu-ume T, Nakamura N, Shino K, Toritsuka Y, Horibe S, Ochi T (1997) Temporal and spatial expression of transforming growth factor-beta in the healing patellar ligament of the rat. J Orthop Res 15(6):837–843

    Article  PubMed  CAS  Google Scholar 

  • Nedelec B, Ghahary A, Scott PG, Tredget EE (2000) Control of wound contraction. Basic and clinical features. Hand Clin 16(2):289–302

    PubMed  CAS  Google Scholar 

  • Niyibizi C, Kavalkovich K, Yamaji T, Woo SL (2000) Type V collagen is increased during rabbit medial collateral ligament healing. Knee Surg Sports Traumatol Arthrosc 8(5):281–285

    Article  PubMed  CAS  Google Scholar 

  • Ono I, Yamashita T, Hida T, Jin HY, Ito Y, Hamada H, Akasaka Y, Ishii T, Jimbow K (2004) Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds. J Surg Res 120(1):47–55

    Article  PubMed  CAS  Google Scholar 

  • Phisitkul P, James SL, Wolf BR, Amendola A (2006) MCL injuries of the knee: current concepts review. Iowa Orthop J 26:77–90

    PubMed  Google Scholar 

  • Reider B, Sathy MR, Talkington J, Blyznak N, Kollias S (1994) Treatment of isolated medial collateral ligament injuries in athletes with early functional rehabilitation. A five-year follow-up study. Am J Sports Med 22(4):470–477

    Article  PubMed  CAS  Google Scholar 

  • Sakai H, Koibuchi N, Ohtake H, Tamai K, Fukui N, Oda H, Saotome K (2001) Type I and type III procollagen gene expressions in the early phase of ligament healing in rabbits: an in situ hybridization study. J Orthop Res 19(1):132–135

    Article  PubMed  CAS  Google Scholar 

  • Smith PC, Caceres M, Martinez J (2006) Induction of the myofibroblastic phenotype in human gingival fibroblasts by transforming growth factor-beta1: role of RhoA-ROCK and c-Jun N-terminal kinase signaling pathways. J Periodontal Res 41(5):418–425

    Article  PubMed  CAS  Google Scholar 

  • Smith CA, Stauber F, Waters C, Alway SE, Stauber WT (2007) Transforming growth factor-beta following skeletal muscle strain injury in rats. J Appl Physiol 102(2):755–761

    Article  PubMed  CAS  Google Scholar 

  • Xu G, Bochaton-Piallat ML, Andreutti D, Low RB, Gabbiani G, Neuville P (2001) Regulation of alpha-smooth muscle actin and CRBP- 1 expression by retinoic acid and TGF-beta in cultured fibroblasts. J Cell Physiol 187(3):315–325

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Liu Y (2002) Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J Am Soc Nephrol 13(1):96–107

    Article  PubMed  CAS  Google Scholar 

  • Yang J, Dai C, Liu Y (2003) Hepatocyte growth factor suppresses renal interstitial myofibroblast activation and intercepts Smad signal transduction. Am J Pathol 163(2):621–632

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from the Natural Science Foundation of Heilongjiang (D200618). We would also like to thank Jiyou Sun for his help with the statistical analysis.

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Correspondence to Zhaozhu Li.

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Jiang, D., Jiang, Z., Han, F. et al. HGF suppresses the production of collagen type III and α-SMA induced by TGF-β1 in healing fibroblasts. Eur J Appl Physiol 103, 489–493 (2008). https://doi.org/10.1007/s00421-008-0733-7

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  • DOI: https://doi.org/10.1007/s00421-008-0733-7

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