miR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1
Open Access
- 4 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 4 (1), 1-17
- https://doi.org/10.1038/s42003-020-01516-w
Abstract
Diabetic kidney disease (DKD) is a major complication of diabetes. Expression of members of the microRNA (miRNA) miR-379 cluster is increased in DKD. miR-379, the most upstream 5′-miRNA in the cluster, functions in endoplasmic reticulum (ER) stress by targeting EDEM3. However, the in vivo functions of miR-379 remain unclear. We created miR-379 knockout (KO) mice using CRISPR-Cas9 nickase and dual guide RNA technique and characterized their phenotype in diabetes. We screened for miR-379 targets in renal mesangial cells from WT vs. miR-379KO mice using AGO2-immunopreciptation and CLASH (cross-linking, ligation, sequencing hybrids) and identified the redox protein thioredoxin and mitochondrial fission-1 protein. miR-379KO mice were protected from features of DKD as well as body weight loss associated with mitochondrial dysfunction, ER- and oxidative stress. These results reveal a role for miR-379 in DKD and metabolic processes via reducing adaptive mitophagy. Strategies targeting miR-379 could offer therapeutic options for DKD.This publication has 60 references indexed in Scilit:
- Mapping the Human miRNA Interactome by CLASH Reveals Frequent Noncanonical BindingCell, 2013
- Autophagy in proximal tubules protects against acute kidney injuryKidney International, 2012
- A Resource for the Conditional Ablation of microRNAs in the MouseCell Reports, 2012
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- TGF-β activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTENNature, 2009
- Argonaute HITS-CLIP decodes microRNA–mRNA interaction mapsNature, 2009
- TopHat: discovering splice junctions with RNA-SeqBioinformatics, 2009
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectNature, 2007
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005
- An economic method for the fluorescent labeling of PCR fragmentsNature Biotechnology, 2000