PGC1α is required for the renoprotective effect of lncRNA Tug1 in vivo and links Tug1 with urea cycle metabolites.

ABSTRACT: lncRNA taurine-upregulated gene 1 (Tug1) is a promising therapeutic target in the progression of diabetic nephropathy (DN), but the molecular basis of its protection remains poorly understood. Here, we generate a triple-mutant diabetic mouse model coupled with metabolomic profiling data to interrogate whether Tug1 interaction with peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) is required for mitochondrial remodeling and progression of DN in vivo. We find that, compared with diabetic conditional deletion of Pgc1α in podocytes alone (db/db; Pgc1α^Pod-f/f), diabetic Pgc1α knockout combined with podocyte-specific Tug1 overexpression (db/db; Tug^PodTg; Pgc1α^Pod-f/f) reverses the protective phenotype of Tug1 overexpression, suggesting that

SUBMITTER: Li L 

PROVIDER: S-EPMC8369494 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature