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缺氧诱导因子-1α与微小 RNA 在急性肾损伤中的相互作用。

The crosstalk between hypoxia-inducible factor-1α and microRNAs in acute kidney injury.

机构信息

Division of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Exp Biol Med (Maywood). 2020 Mar;245(5):427-436. doi: 10.1177/1535370220902696. Epub 2020 Jan 29.

Abstract

UNLABELLED

Acute kidney injury (AKI) is a common critical clinical disease that is characterized by a rapid decline in renal function and reduced urine output. Ischemia and hypoxia are dominant pathophysiological changes in AKI that are induced by many factors, and the role of the “master” regulator hypoxia-inducible factor-1α (HIF-1α) is well recognized in AKI-related studies. MicroRNAs have been found to act as critical regulators of AKI pathophysiological process. More studies now have reported mutual interactions between HIF-1α and microRNAs in AKI. Therefore, in this brief review, we look into the mutual regulatory mechanisms between HIF-1α and microRNAs and discuss their function in the process of AKI. Recent studies demonstrated that HIF-1α is involved in the regulation of multiple functional microRNAs in AKI, and in turn, the level of HIF-1α is regulated by specific microRNAs. However, the role of the interactions between HIF-1α and microRNAs in AKI are controversial, and whether interventions targeting relevant mechanisms could achieve clinical benefits is not clear. Much work remains to further explore the value of targeting the HIF-1α-microRNA pathway in AKI treatment.

IMPACT STATEMENT

At first, we have discussed the role of hypoxia-inducible factor-1α (HIF-1α) and microRNAs in the acute kidney injury (AKI) pathophysiology. Then we have summarized the interactions between HIF-1α and microRNAs reported by AKI-related studies and concluded their regulatory effects in AKI process. Finally, we have made a vision of HIF-1α/microRNAs pathway’s potential as the intervention target in AKI. The mini review provides a systematic understanding of the crosstalk between HIF-1α and microRNAs in AKI and their effects on AKI pathophysiology and treatment.

摘要

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急性肾损伤(AKI)是一种常见的危重病,其特征是肾功能迅速下降和尿量减少。缺血和缺氧是 AKI 的主要病理生理变化,由多种因素引起,在 AKI 相关研究中,“主”调节因子缺氧诱导因子-1α(HIF-1α)的作用得到了很好的认识。现已发现 microRNAs 可作为 AKI 病理生理过程的关键调节因子。越来越多的研究报告称,HIF-1α 和 microRNAs 之间存在相互作用。因此,在本综述中,我们研究了 HIF-1α 和 microRNAs 之间的相互调节机制,并讨论了它们在 AKI 过程中的功能。最近的研究表明,HIF-1α 参与 AKI 中多种功能 microRNAs 的调节,反过来,HIF-1α 的水平受特定 microRNAs 的调节。然而,HIF-1α 和 microRNAs 之间相互作用在 AKI 中的作用存在争议,针对相关机制的干预是否能带来临床获益尚不清楚。还有很多工作要做,以进一步探讨针对 AKI 治疗中 HIF-1α-microRNA 途径的靶向作用的价值。

重点说明

首先,我们讨论了缺氧诱导因子-1α(HIF-1α)和 microRNAs 在急性肾损伤(AKI)病理生理学中的作用。然后,我们总结了 AKI 相关研究中报道的 HIF-1α 和 microRNAs 之间的相互作用,并得出了它们在 AKI 过程中的调节作用。最后,我们对 HIF-1α/microRNAs 途径作为 AKI 干预靶点的潜力进行了展望。该综述提供了对 HIF-1α 和 microRNAs 在 AKI 中的相互作用及其对 AKI 病理生理学和治疗的影响的系统认识。

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