PPARγ激动剂对成人正常皮肤成纤维细胞转分化的作用

目的：观察过氧化物酶体增殖物激活受体γ（PPARγ）激动剂对转化生长因子β1（TGF-β1）诱导成纤维细胞转分化的影响,探讨其抗瘢痕纤维化的潜在作用。方法：体外培养成人正常皮肤成纤维细胞,利用免疫荧光细胞化学法观察、分析PPARγ配体15-脱氧前列腺素J2（15d-PGJ2）及其激动剂曲格列酮对TGF-β1诱导的α平滑肌动蛋白（α-SMA）表达的影响,利用Western blot、实时荧光RT-PCR技术检测PPARγ激动剂对TGF-β1诱导的α-SMA蛋白及mRNA水平的影响。结果：TGF-β1能显著增加成纤维细胞转分化为肌成纤维细胞;与TGF-β1诱导组相比,10μM曲格列酮、15d-PGJ2预处理组的α-SMA表达量显著减少（P〈0.01）,抑制效应分别为31%、57%;预处理组的α-SMA mRNA水平显著下降（P〈0.01）。结论：PPARγ激动剂能抑制TGF-β1诱导的成人正常皮肤成纤维细胞的转分化的效应,具有抗皮肤瘢痕化、挛缩的潜在作用。

Effects of PPARγ agonists On TOF-β1-induced transdifferentiation in normal skin fibroblasts in vitro

Objective To observe the effects of peroxisome prolilerator-activated receptor γ （PPARγ） agonists on TGFβ1-induced transdifferentiation of the cultured the normal skin fibroblasts in vitro,so as to explore its effects on inhibiting the formation of hypertrophic scars.Methods In cultured normal skin fibroblasts,the effects of both natural （15d-PGJ2） and synthetic （troglitazone） PPARγ agonists on the level of TGF-β1-indued α-smooth muscle actin expression were assessed by immunofluorescence and image analysis.The effects of PPARγ agonists on the level of α-smooth muscle actin expression induced by TGF-β1 were detected by Western blot.Results In normal skin fibroblasts,TGF-β1 enhanced transdifferentiation of fibroblasts to myofibroblasts.The level of α-SMA expression in 15d-PGJ2 and troglitazone-pretreated groups respectively were significantly decreased compared with TGF-β1-stimulated group （P〈0.01）.Conclusion PPARγ agonists may inhibit the profibrotic activities of TGF-β1 on skin fibroblasts：myofibroblast differentiation.Thus PPARγ agonists have novel and potent antifibrotic effects in human skin fibroblasts and may have potential for therapy of hypertrophic scar.