microRNA are Central Players in Anti- and Profibrotic Gene Regulation during Liver Fibrosis.
microRNA are Central Players in Anti- and Profibrotic Gene Regulation during Liver Fibrosis.
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DOI：
10.3389/fphys.2012.00049
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发表时间：
2012
影响因子：
4
通讯作者：
Odenthal M
中科院分区：
文献类型：
--
作者：
Noetel A;Kwiecinski M;Elfimova N;Huang J;Odenthal M
microRNA（miRNA）是一类非编码RNA，通过靶向转录本的3′-非翻译区（3′-UTR），在转录后影响mRNA的稳定性和翻译。因此，miRNA的失调影响广泛的细胞过程，例如参与器官重塑过程的细胞增殖和分化。在各种病因的慢性肝病中观察到不同的miRNA模式。慢性肝病导致不受控制的瘢痕形成，最终导致肝纤维化甚至肝硬化。由于已经显示miR-29失调涉及细胞外基质蛋白的合成，因此miR-29是特别感兴趣的。体内数据强调了miR-29在肝胶原稳态中的重要性，这些数据显示实验性严重纤维化与显著的miR-29减少相关。miR-29的丢失是由于肝星状细胞对暴露于促纤维化介质TGF-β和PDGF-BB的反应。Smad蛋白和Ap 1复合物的几个假定结合位点位于miR-29启动子中，这被认为介导了纤维化中miR-29的减少。其他miRNA在促纤维化刺激后高度增加，例如miR-21。在TGF-β刺激后，miR-21响应于Smad-3而不是Smad-2活化而转录上调。此外，TGF-β通过形成含有Smad蛋白的微处理器复合物促进miR-21表达。然后，升高的miR-21可通过其对TGF-β抑制性Smad-7蛋白的抑制而充当促纤维化miRNA。
MicroRNA (miRNA) are small non-coding RNA molecules that posttranscriptionally effect mRNA stability and translation by targeting the 3′-untranslated region (3′-UTR) of various transcripts. Thus, dysregulation of miRNA affects a wide range of cellular processes such as cell proliferation and differentiation involved in organ remodeling processes. Divergent miRNA patterns were observed during chronic liver diseases of various etiologies. Chronic liver diseases result in uncontrolled scar formation ending up in liver fibrosis or even cirrhosis. Since it has been shown that miR-29 dysregulation is involved in synthesis of extracellular matrix proteins, miR-29 is of special interest. The importance of miR-29 in hepatic collagen homeostasis is underlined by in vivo data showing that experimental severe fibrosis is associated with a prominent miR-29 decrease. The loss of miR-29 is due to the response of hepatic stellate cells to exposure to the profibrogenic mediators TGF-β and PDGF-BB. Several putative binding sites for the Smad proteins and the Ap1 complex are located in the miR-29 promoter, which are suggested to mediate miR-29 decrease in fibrosis. Other miRNA are highly increased after profibrogenic stimulation, such as miR-21. miR-21 is transcriptionally upregulated in response to Smad-3 rather than Smad-2 activation after TGF-β stimulation. In addition, TGF-β promotes miR-21 expression by formation of a microprocessor complex containing Smad proteins. Elevated miR-21 may then act as a profibrogenic miRNA by its repression of the TGF-β inhibitory Smad-7 protein.
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影响因子：
29.4
作者：
Knittel, T;Kobold, D;Ramadori, G
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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