title: HGF inhibits TGF-β1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat.
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.
authors.affiliation: Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150086, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Cui
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Jiang
authors.forename: Lihui
authors.initials: L
authors.lastname: Qu
authors.forename: Junbin
authors.initials: J
authors.lastname: Guo
authors.forename: Zhaozhu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000125:Achilles Tendon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000378:metabolism*; D024022:Fibrillar Collagens / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007267:Injections; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D058628:Myofibroblasts / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D024022:Fibrillar Collagens; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D020778:Matrix Metalloproteinase 2