PGC1α is required for the renoprotective effect of lncRNA Tug1 in vivo and links Tug1 with urea cycle metabolites.
PGC1α is required for the renoprotective effect of lncRNA Tug1 in vivo and links Tug1 with urea cycle metabolites.
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PGC1α是lncRNA Tug 1在体内发挥肾保护作用所必需的，并将Tug 1与尿素循环代谢产物联系起来。
DOI：
10.1016/j.celrep.2021.109510
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发表时间：
2021-08-10
期刊：
影响因子：
8.8
通讯作者：
Danesh FR
中科院分区：
文献类型：
--
作者：
Li L;Long J;Mise K;Galvan DL;Overbeek PA;Tan L;Kumar SV;Chan WK;Lorenzi PL;Chang BH;Danesh FR
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; Pgc1αPod-f/f), diabetic Pgc1α knockout combined with podocyte-specific Tug1 overexpression (db/db; TugPodTg; Pgc1αPod-f/f) reverses the protective phenotype of Tug1 overexpression, suggesting that PGC1α is required for the renoprotective effect of Tug1. Using unbiased metabolomic profiling, we find that altered urea cycle metabolites and mitochondrial arginase 2 play an important role in Tug1/PGC1α-induced mitochondrial remodeling. Our work identifies a functional role of the Tug1/PGC1α axis on mitochondrial metabolic homeostasis and urea cycle metabolites in experimental models of diabetes. Li et al. show that PGC1α is required for the protective effects of lncRNA Tug1 on mitochondrial function in podocytes and progression of diabetic nephropathy in vivo. They find that altered urea cycle metabolites and mitochondrial arginase 2 (Arg2) play important roles in Tug1/PGC1α-induced mitochondrial remodeling.
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影响因子：
13.6
作者：
Ayanga, Bernard A.;Badal, Shawn S.;Danesh, Farhad R.
通讯作者：
Danesh, Farhad R.
影响因子：
64.5
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20.8
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影响因子：
64.5
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