METTL3/mA/miRNA-873-5p Attenuated Oxidative Stress and Apoptosis in Colistin-Induced Kidney Injury by Modulating Keap1/Nrf2 Pathway

Overview

Journal Front Pharmacol

Date 2019 Jun 4

PMID 31156435

Citations 78

Authors

Jian Wang

Muhammad Ishfaq

Liang Xu

Chunli Xia

Chunli Chen

Jichang Li

Affiliations

Soon will be listed here.

Abstract

Nephrotoxicity of colistin is the major factor limiting its clinical application. However, the exact mechanism of colistin-induced nephrotoxicity is still elusive. N-Methyladenosine (mA) modification has been implicated in many biological processes, however, its role in colistin-induced nephrotoxicity needs to be elucidated. Mouse renal tubular epithelial cells (mRTECs) were treated with 200 μM colistin with or without METTL3 overexpression. Cells injury, mA assay, oxidative stress and apoptosis were examined. Levels of mA are decreased after colistin treatment in mRTECs. METTL3 is the major factor involved in abnormal mA modification. METTL3 overexpression plays a protective role against colistin-induced oxidative stress and apoptosis. Moreover, METTL3 interacts with the microprocessor protein DGCR8 and positively modulates miR-873-5p mature process in an mA-dependent manner. Further experiments show that miR-873-5p could regulate Keap1-Nrf2 pathway against colistin-induced oxidative stress and apoptosis. These studies revealed an important role of METTL3/mA in colistin-induced nephrotoxicity and provide a new insight on mA modification in drug induced toxicity.

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