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- Title
miR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1.
- Authors
Kato, Mitsuo; Abdollahi, Maryam; Tunduguru, Ragadeepthi; Tsark, Walter; Chen, Zhuo; Wu, Xiwei; Wang, Jinhui; Chen, Zhen Bouman; Lin, Feng-Mao; Lanting, Linda; Wang, Mei; Huss, Janice; Fueger, Patrick T; Chan, David; Natarajan, Rama
- 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. Kato, Abdollahi et al. identify a redox protein thioredoxin and mitochondrial fission-1 (FIS1) protein as miR-379 targets in mouse kidney. They find that miR-379 knockout mice are protected from diabetic kidney disease by enhancing mitophagy via FIS1, suggesting miR-379 as a potential therapeutic target for diabetic kidney disease.
- Subjects
DIABETIC nephropathies; MICRORNA; ENDOPLASMIC reticulum; MITOCHONDRIAL pathology; CRISPRS; THIOREDOXIN
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-020-01516-w