TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21.
TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21.
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DOI：
10.1038/srep32231
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发表时间：
2016-08-24
影响因子：
4.6
通讯作者：
Xiao Z
中科院分区：
文献类型：
--
作者：
Liu Y;Li Y;Li N;Teng W;Wang M;Zhang Y;Xiao Z
TGF-β1在疤痕组织中表达上调，促进真皮成纤维细胞的增殖、胶原形成和分化。 miR-21是首先在人类基因组中发现的microRNA之一。本研究的目的是探讨miR-21在TGF-β1诱导的疤痕成纤维细胞增殖和转分化中的机制。在本研究中，我们首先发现TGF-β1通过上调miR-21表达促进疤痕成纤维细胞增殖和转分化，而当抑制miR-21时，这种表达可以减弱。 miR-21 的过表达对增殖和转分化具有与 TGF-β1 类似的作用。此外，TGF-β1 增加了瘢痕疙瘩成纤维细胞中 MMP2 和 MMP9 的表达和活性，而这种表达和活性可被 miR-21 抑制所抑制。最后，结果证明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促进瘢痕疙瘩成纤维细胞增殖和转分化，PTEN/AKT信号通路在此过程中发挥重要作用，这为皮肤疤痕的临床治疗提供了潜在的理论依据。
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.