Effects of hepatocyte growth factor on collagen synthesis and matrix metalloproteinase production in keloids.

Effects of hepatocyte growth factor on collagen synthesis and matrix metalloproteinase production in keloids.
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DOI:
10.3346/jkms.2011.26.8.1081
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发表时间:
2011-08
影响因子:
4.5
通讯作者:
Rah DK
Rah DK
中科院分区:
医学4区
文献类型:
--
作者:
Lee WJ;Park SE;Rah DK

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疤痕疙瘩是由于胶原蛋白过度生成和沉积而导致的皮肤真皮层的病理性增生。肝细胞生长因子 (HGF) 增加基质金属蛋白酶 (MMP)-1 的表达并抑制胶原蛋白合成,从而调节细胞外基质周转。为了研究 HGF 的抗纤维化作用,我们检测了添加不同量的 HGF 蛋白后,人真皮成纤维细胞 (HDF) 细胞系和瘢痕疙瘩成纤维细胞 (KFs,n = 5) 中 I 型和 III 型胶原蛋白和基质金属蛋白酶 (MMP-1、MMP-3) 的 mRNA 表达。我们还通过酶谱法评估了 MMP-2、MMP-9 的酶活性。同时用TGF-β1和HGF蛋白处理的HDF中,I型和III型胶原mRNA表达均显着降低(P < 0.05)。 MMP-1、MMP-3 mRNA表达也下降。然而,随着HGF用量的增加,KF中MMP-1、MMP-3 mRNA的表达显着增加,且呈剂量依赖性(P < 0.05)。 MMP-2的酶活性随着HGF蛋白的增加而增加,且呈剂量依赖性。然而,MMP-9的酶活性没有改变。这些结果表明,HGF 的抗纤维化作用可能通过逆转病理性纤维化对疤痕疙瘩产生治疗作用。
Keloids are pathologic proliferations of the dermal layer of the skin resulting from excessive collagen production and deposition. Hepatocyte growth factor (HGF) increases the expression of matrix metalloproteinase (MMP)-1 and suppresses collagen synthesis to modulate extracellular matrix turnover. To investigate the anti-fibrotic effects of HGF, we examine the mRNA expression of collagen types I and III and matrix metalloproteinase (MMP-1, MMP-3) on human dermal fibroblast (HDF) cell lines and keloid fibroblasts (KFs, n = 5) after adding various amount of HGF protein. We also evaluated the enzymatic activity of MMP-2, MMP-9 by zymograghy. In HDFs treated with TGF-β1 and HGF protein simultaneously, both type I and III collagen mRNA expression significantly decreased (P < 0.05). Expression of MMP-1, MMP-3 mRNA also decreased. However, the mRNA expression of MMP-1, MMP-3 significantly increased in KFs with increasing amount of HGF in dose dependent manner (P < 0.05). The enzymatic activities of MMP-2 increased with increasing HGF protein in a dose-dependent manner. However, the enzymatic activity of MMP-9 did not change. These results suggest that the anti-fibrotic effects of HGF may have therapeutic effects on keloids by reversing pathologic fibrosis.
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