This review highlights new developments in miRNA as diagnostic and surveillance tools in diseases damaging the renal proximal tubule mediated by endothelin in the field of renal carcinoma, proteinuric kidney disease and tubulotoxicity. A new mechanism in the miRNA regulation of proteins leads to the binding of the miRNA directly to the DNA with premature transcriptional termination and hence the formation of truncated protein isoforms (Mxi2, Vim3). These isoforms are mediated through miRNA15a or miRNA 498, respectively. ET‐1 can activate a cytoplasmic complex consisting of NF‐κB p65, MAPK p38α, and PKCα. Consequently, PKCα does not transmigrate into the nucleus, which leads to the loss of suppression of a primiRNA15a, maturation of this miRNA in the cytoplasm, tubular secretion and detectability in the urine. This mechanism has been shown in renal cell carcinoma and in proteinuric disease as a biomarker for the activation of the signalling pathway. Similarly, ET‐1 induced miRNA 498 transmigrates into the nucleus to form the truncated protein Vim3, which is a biomarker for the benign renal cell tumour, oncocytoma. In tubulotoxicity, ET‐1 induced miRNa133a down‐regulating multiple‐drug‐resistant related protein‐2, relevant for proteinuric and cisplatin/cyclosporine A toxicity. Current advantages and limitations of miRNAs as urinary biomarkers are discussed.

中文翻译：

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MicroRNAs 作为监测 Endothelin-1 信号传导和肾脏疾病潜在治疗的标志物：癌 - 蛋白尿损伤 - 毒性。（审查）

这篇综述重点介绍了 miRNA 作为诊断和监测工具的新进展，该工具可用于肾癌、蛋白尿性肾病和肾小管毒性领域内皮素介导的损害肾近端小管的疾病。miRNA 调控蛋白质的一种新机制导致 miRNA 直接与 DNA 结合，但会提前终止转录，从而形成截短的蛋白质亚型（Mxi2、Vim3）。这些同种型分别通过 miRNA15a 或 miRNA 498 介导。ET-1 可以激活由 NF-κB p65、MAPK p38α 和 PKCα 组成的细胞质复合物。因此，PKCα 不会迁移到细胞核中，这导致 primiRNA15a 的抑制丧失、该 miRNA 在细胞质中的成熟、肾小管分泌和尿液中的可检测性。这种机制已在肾细胞癌和蛋白尿疾病中显示为信号通路激活的生物标志物。类似地，ET-1 诱导 miRNA 498 迁移到细胞核中形成截短蛋白 Vim3，这是良性肾细胞肿瘤嗜酸细胞瘤的生物标志物。在肾小管毒性方面，ET-1 诱导 miRNa133a 下调多重耐药相关蛋白 2，与蛋白尿和顺铂/环孢素 A 毒性相关。讨论了 miRNA 作为尿液生物标志物的当前优势和局限性。ET-1 诱导 miRNa133a 下调多重耐药相关蛋白-2，与蛋白尿和顺铂/环孢素 A 毒性相关。讨论了 miRNA 作为尿液生物标志物的当前优势和局限性。ET-1 诱导 miRNa133a 下调多重耐药相关蛋白-2，与蛋白尿和顺铂/环孢素 A 毒性相关。讨论了 miRNA 作为尿液生物标志物的当前优势和局限性。