Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, People's Republic of China.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, People's Republic of China.
Sci Rep. 2016 Aug 24;6:32231. doi: 10.1038/srep32231.
TGF-β1, upregulated in keloid tissue, promotes the proliferation, collagen formation and differentiation of dermal fibroblasts. miR-21 is one of microRNAs first found in human genome. The aim of our study is to explore the mechanisms of miR-21 in TGF-β1-induced scar fibroblasts proliferation and transdifferentiation. In the present study, first we found that TGF-β1 promoted scar fibroblasts proliferation and transdifferentiation via up-regulating miR-21 expression, which could be attenuated when miR-21 was inhibited. Overexpression of miR-21 had similar effect as TGF-β1 on proliferation and transdifferentiation. Additionally, TGF-β1 increased the expressions and activities of MMP2 and MMP9 in keloid fibroblasts, which was suppressed by miR-21 inhibition. Finally, the results demonstrated that PTEN/AKT signaling pathway played important role in TGF-β1-induced transdifferentiation. In conclusion, our study suggests that TGF-β1 promotes keloid fibroblasts proliferation and transdifferentiation via up-regulation of miR-21 and PTEN/AKT signalling pathway plays important role in this process, which provides a potential theoretical basis for clinical treatment of skin scars.
TGF-β1 在瘢痕组织中上调,促进真皮成纤维细胞的增殖、胶原形成和分化。miR-21 是人类基因组中首次发现的 microRNA 之一。我们的研究旨在探讨 miR-21 在 TGF-β1 诱导的瘢痕成纤维细胞增殖和转分化中的作用机制。在本研究中,首先发现 TGF-β1 通过上调 miR-21 表达促进瘢痕成纤维细胞增殖和转分化,当抑制 miR-21 时可减弱这种作用。miR-21 的过表达对增殖和转分化具有与 TGF-β1 相似的作用。此外,TGF-β1 增加了瘢痕成纤维细胞中 MMP2 和 MMP9 的表达和活性,而 miR-21 抑制可抑制这种作用。最后,结果表明,PTEN/AKT 信号通路在 TGF-β1 诱导的转分化中发挥重要作用。总之,我们的研究表明,TGF-β1 通过上调 miR-21 促进瘢痕成纤维细胞的增殖和转分化,PTEN/AKT 信号通路在这个过程中起重要作用,为皮肤瘢痕的临床治疗提供了潜在的理论基础。