PMID- 21165643 OWN - NLM STAT- MEDLINE DCOM- 20111108 LR - 20211020 IS - 1439-6327 (Electronic) IS - 1439-6319 (Linking) VI - 111 IP - 7 DP - 2011 Jul TI - HGF inhibits TGF-beta1-induced myofibroblast differentiation and ECM deposition via MMP-2 in Achilles tendon in rat. PG - 1457-63 LID - 10.1007/s00421-010-1764-4 [doi] AB - 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 mul(-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-beta1) induced fibrogenic responses in primary Achilles tendon fibroblasts in rats, HGF treatment for 24 h reduced alpha-smooth muscle actin (alpha-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 alpha-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-beta1-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. FAU - Cui, Qingbo AU - Cui Q AD - Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150086, China. FAU - Wang, Zhigang AU - Wang Z FAU - Jiang, Dapeng AU - Jiang D FAU - Qu, Lihui AU - Qu L FAU - Guo, Junbin AU - Guo J FAU - Li, Zhaozhu AU - Li Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101217 PL - Germany TA - Eur J Appl Physiol JT - European journal of applied physiology JID - 100954790 RN - 0 (Fibrillar Collagens) RN - 0 (Transforming Growth Factor beta1) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Achilles Tendon/cytology/*drug effects/metabolism/physiology MH - Animals MH - Cell Differentiation/*drug effects MH - Cells, Cultured MH - Drug Evaluation, Preclinical MH - Extracellular Matrix/*metabolism MH - Fibrillar Collagens/metabolism MH - Hepatocyte Growth Factor/*pharmacology MH - Injections MH - Male MH - Matrix Metalloproteinase 2/metabolism/*physiology MH - Mice MH - Myofibroblasts/*drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Transforming Growth Factor beta1/*pharmacology MH - Up-Regulation/drug effects EDAT- 2010/12/18 06:00 MHDA- 2011/11/09 06:00 CRDT- 2010/12/18 06:00 PHST- 2010/11/27 00:00 [accepted] PHST- 2010/12/18 06:00 [entrez] PHST- 2010/12/18 06:00 [pubmed] PHST- 2011/11/09 06:00 [medline] AID - 10.1007/s00421-010-1764-4 [doi] PST - ppublish SO - Eur J Appl Physiol. 2011 Jul;111(7):1457-63. doi: 10.1007/s00421-010-1764-4. Epub 2010 Dec 17.