MicroRNAs and fibrosis.
MicroRNAs and fibrosis.
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DOI：
10.1097/mnh.0b013e328354e559
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发表时间：
2012-07
影响因子：
3.2
通讯作者：
Noureddine L
中科院分区：
文献类型：
--
作者：
Patel V;Noureddine L
MicroRNAs(MiRNAs)是一种短的非编码RNA，可以抑制植物和动物的基因表达。MiRNAs已经成为哺乳动物生物学几乎所有方面的关键参与者。在糖尿病、高胆固醇血症、癌症和组织纤维化等多种人类疾病中观察到miRNA的异常表达。因此，纠正miRNA表达的方法代表了治疗这些疾病的新策略。MiRNAs对肾脏发育和动态平衡是必不可少的。在小鼠肾纤维化模型中观察到miRNA的异常表达。三个受转化生长因子-β调控的miRNA家族，miR-21、miR-200和miR-29已被证明调节肾纤维化。MIR-21通过前馈循环，放大转化生长因子-β信号，促进纤维化。相反，miR-200和miR-29分别通过抑制上皮-间质转化和防止细胞外基质沉积来减少纤维化。抑制miR-21表达或增强miR-29表达可预防小鼠肾脏纤维化。MiRNA的异常表达扰乱了导致肾纤维化进展的信号通路。因此，miRNAs是治疗肾纤维化的新的生物标志物和治疗靶点。
MicroRNAs (miRNAs) are short noncoding RNAs that inhibit gene expression in plants and animals. miRNAs have emerged as key players in virtually all aspects of mammalian biology. Aberrant miRNA expression is observed in numerous human diseases such as diabetes, hypercholesterolemia, cancer, and tissue fibrosis. Therefore, approaches to correct miRNA expression represent the novel therapeutic strategies for these diseases. miRNAs are essential for kidney development and homeostasis. Aberrant miRNA expression is observed in the mouse models of kidney fibrosis. Three TGF-β-regulated miRNA families, miR-21, miR-200, and miR-29 have been shown to modulate renal fibrosis. miR-21, through a feed-forward loop, amplifies TGF-β signaling and promotes fibrosis. Conversely, miR-200 and miR-29 reduce fibrosis by inhibiting epithelial-tomesenchymal transition and preventing the deposition of extracellular matrix, respectively. Inhibition of miR-21 expression or augmenting miR-29 expression prevents kidney fibrosis in mice. Aberrant miRNA expression perturbs signaling pathways that lead to progression of kidney fibrosis. Thus, miRNAs represent novel biomarkers and therapeutic targets in the treatment of kidney fibrosis.