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microRNA cascade in diabetic kidney disease: Big impact initiated by a small RNA.

机译:microRNA级联在糖尿病性肾脏疾病中:小RNA引发的巨大影响。

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level by-blocking translation or promoting cleavage of their target mRNAs. Almost 1,000 human miRNAs have been identified that target and downregulate at least 60% of human protein-coding genes expressed in the genome. Accumulating evidence suggests that miRNAs play important roles in various diseases including cancers, diabetes and kidney dysfunction. In particular, key miRNAs were upregu-lated in the kidneys of diabetic mice. Furthermore, podocyte-specific deletion of Dicer, an essential enzyme involved in the processing of miRNAs, led to progressive renal glomerular and tubular damage in mice. Diabetic nephropathy (DN) is a progressive kidney disease and one of most common complications in diabetes. It is characterized by glomerular basement membrane thickening, mesangial expansion (hypertrophy), extracellular matrix (ECM) accumulation and podocyte dysfunction. Transforming growth factor-beta1 (TGF(i) is increased in renal cells during DN progression and has been implicated in these events. miR-192,amiRNAhighly expressed in the kidney, was increased in the renal glomeruli of diabetic mice and in glomerular mesangial cells (MC) treated with TGFbeta, and could induce type I collagen alpha2 chain (Colla2) gene by inhibiting ZEB1 and ZEB2 (E-box repres-sors). In another study, miR-377 could increase fibronectin in MCs by targeting PAK1 and MnSOD.
机译:MicroRNA(miRNA)是短的非编码RNA,可通过阻止翻译或促进其靶mRNA的切割来调节转录后水平的基因表达。已经鉴定出近1,000种人类miRNA,它们靶向并下调基因组中表达的至少60%的人类蛋白质编码基因。越来越多的证据表明,miRNA在各种疾病(包括癌症,糖尿病和肾功能不全)中起重要作用。特别地,关键的miRNA在糖尿病小鼠的肾脏中被上调。此外,Dicer足细胞特异性缺失,Dicer是参与miRNA加工的必需酶,可导致小鼠进行性肾小球和肾小管损害。糖尿病肾病(DN)是一种进行性肾脏疾病,是糖尿病中最常见的并发症之一。其特点是肾小球基底膜增厚,肾小球膜扩张(肥大),细胞外基质(ECM)积累和足细胞功能障碍。在DN进程中,肾细胞中转化生长因子β1(TGF(i)增加),并参与了这些事件。在肾脏中高表达的miR-192,amiRNA在糖尿病小鼠的肾小球和肾小球系膜细胞中增加(MC)经过TGFbeta处理后,可以通过抑制ZEB1和ZEB2(E-box代表)诱导I型胶原α2链(Colla2)基因;另一项研究表明,miR-377可以通过靶向PAK1和MnSOD来增加MC中的纤连蛋白。 。

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