Pediatric Orthopedics Unit, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150086, China.
Eur J Appl Physiol. 2011 Jul;111(7):1457-63. doi: 10.1007/s00421-010-1764-4. Epub 2010 Dec 17.
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.
成肌纤维细胞分化和细胞外基质（ECM）沉积是肌腱瘢痕形成的重要组成部分，肝细胞生长因子（HGF）据报道可防止肌腱的纤维生成反应。基质金属蛋白酶-2（MMP-2）也参与肌腱的愈合过程。HGF 是否能保护愈合的跟腱免受损伤诱导的瘢痕形成，其机制尚不清楚。在创伤后 2 周内，每天除非手术对照组外，大鼠跟腱局部注射 HGF（100ng 50μl(-1)每只鼠）或磷酸盐缓冲盐水（PBS）。组织学检查显示 HGF 改善了大鼠手术切口引起的胶原纤维紊乱。在转化生长因子β-1（TGF-β1）诱导大鼠原代跟腱成纤维细胞纤维生成反应后，HGF 治疗 24 小时可降低α-平滑肌肌动蛋白（α-SMA）（0.60±0.07 倍，P<0.05）和 III 型胶原表达（0.39±0.07 倍，P<0.05）。此外，HGF 上调 MMP-2 表达（1.23±0.11 倍，P<0.05）。基质金属蛋白酶抑制剂 1（TIMP-1）部分阻断了 HGF 对α-SMA 表达（从 0.60±0.07 倍到 0.83±0.07 倍，P<0.05）和 III 型胶原表达（从 0.39±0.06 倍到 0.86±0.08 倍，P<0.05）的抑制作用。这些结果表明 HGF 可减弱 TGF-β1 诱导的跟腱纤维生成反应，这是由 MMP-2 介导的。这些结果将有助于开发有效的治疗方法，用于治疗跟腱功能障碍修复。
