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HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat

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Abstract

Both myofibroblast differentiation and extracellular matrix (ECM) deposition are essential components of scar formation in tendons, and hepatocyte growth factor (HGF) is reported to prevent fibrogenic responses in tendons. Matrix metalloproteinases-2(MMP-2) is also involved in the healing process in tendons. Whether HGF protects healed Achilles tendons from injury-induced scar formation and the mechanisms are unknown. Daily for 2 weeks after wounding, except for the non-surgical control group, the Achilles tendons in rats were locally injected with HGF (100 ng 50 μl−1 per mouse) or phosphate-buffered saline (PBS). Histological examination showed HGF ameliorated disorganized collagen fibers caused by surgical incisions in rats. After transforming growth factor beta-1 (TGF-β1) induced fibrogenic responses in primary Achilles tendon fibroblasts in rats, HGF treatment for 24 h reduced α-smooth muscle actin (α-SMA) (0.60 ± 0.07-fold, P < 0.05) and type III collagen expression (0.39 ± 0.07-fold, P < 0.05). Moreover, HGF elevated MMP-2 expression (1.23 ± 0.11-fold, P < 0.05). The MMP-2 inhibitor, tissue inhibitors of metalloproteinase-1 (TIMP-1), partially blocked the inhibitory effects of HGF on α-SMA expression (from 0.60 ± 0.07-fold to 0.83 ± 0.07-fold, P < 0.05) and type III collagen expression (from 0.39 ± 0.06-fold to 0.86 ± 0.08-fold, P < 0.05). These results indicate HGF attenuates TGF-β1-induced fibrogenic responses in Achilles tendon, which was mediated by MMP-2. These results will aid in developing effective therapeutic approaches for the dysfunctional repair in Achilles tendons.

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Acknowledgments

This study was supported by grants from the Scientific Research Foundation of the Department of Health of Heilongjiang (2009-138), the Natural Science Foundation of Heilongjiang Province (D201007/C1613), the Scientific Research Foundation for the Returned Overseas of the Department of Science and Technology of Harbin (2010RFLXS009), and the Scientific Research Foundation for Young People of the Second Hospital of Harbin Medical University (QN2007-18). We would also like to thank Professor Daling Zhu and Professor Xiaobo Tang from the Department of Biopharmaceutical Sciences for their assistance in the western blot.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150086, China

    Qingbo Cui, Dapeng Jiang, Junbin Guo & Zhaozhu Li

  2. Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin, China

    Zhigang Wang

  3. Laboratory of Neural Electrophysiology, Department of Physiology, Harbin Medical University, Harbin, China

    Lihui Qu

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  1. Qingbo Cui
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  2. Zhigang Wang
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  3. Dapeng Jiang
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  5. Junbin Guo
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  6. Zhaozhu Li
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Corresponding author

Correspondence to Zhaozhu Li.

Additional information

Communicated by Susan Ward.

Q. Cui and Z. Wang contributed equally to this work.

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Cui, Q., Wang, Z., Jiang, D. et al. HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat. Eur J Appl Physiol 111, 1457–1463 (2011). https://doi.org/10.1007/s00421-010-1764-4

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