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USP28-regulated mitochondrial homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts [ChIP-seq]

ABSTRACT: The majority of diabetics are susceptible to cardiac dysfunction and heart failure, while conventional drug therapy cannot correct diabetic cardiomyopathy (DCM) progression. Herein, we assessed the potential role and therapeutic value of ubiquitin-specific protease 28 (USP28) on the metabolic vulnerability of DCM. PPARα-/- in the db/db background mice were constructed to check the mechanism of USP28 in vivo. Inducible cardiac-specific deletion of Mfn2 in the db/db background mice was utilized to evaluate USP28-mediated cardioprotection. chromatin immunoprecipitation (ChIP) assays revealed that PPARα promote mitofusin 2 (Mfn2) transcription, thereby impeding mitochondrial morphofunctional defects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244905 | GEO | 2023/10/15

REPOSITORIES: GEO

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USP28 Serves as A Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart [RNA-seq]

Project description:The majority of diabetics are susceptible to cardiac dysfunction and heart failure, while conventional drug therapy cannot correct diabetic cardiomyopathy (DCM) progression. Herein, we assessed the potential role and therapeutic value of ubiquitin-specific protease 28 (USP28) on the metabolic vulnerability of DCM. cardiac USP28 deficient diabetic mice showed cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared to their controls. Conversely, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Mechanistically, USP28 directly interacted with peroxisome proliferator-activated receptor α (PPARα), deubiquitinating and stabilizing PPARα (Lys152) to promote mitofusin 2 (Mfn2) transcription, thereby impeding mitochondrial morphofunctional defects.

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USP28-regulated mitochondrial homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts [ChIP-seq]

Project description:USP28-regulated mitochondrial homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts [ChIP-seq]

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2015-05-01 | E-GEOD-59354 | biostudies-arrayexpress

Dual regulation of Fbw7 function and oncogenic transformation by Usp28

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