Hyperglycemia induces skeletal muscle atrophy via a WWP1/KLF15 axis

Autor: Yuko Okada, Wataru Ogawa, Shin'ichi Takeda, Tetsuya Hosooka, Kenta Kobayashi, Yasuhiko Minokoshi, Michihiro Imamura, Yoko Senga, Kazuhiro Nomura, Shiki Okamoto, Yu Hirata
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
KLF15
Mice
0302 clinical medicine
Glucosides
Chlorocebus aethiops
Mice
Knockout
biology
General Medicine
Muscle atrophy
Ubiquitin ligase
Up-Regulation
Muscular Atrophy
medicine.anatomical_structure
030220 oncology & carcinogenesis
COS Cells
Female
medicine.symptom
Research Article
Signal Transduction
medicine.medical_specialty
Ubiquitin-Protein Ligases
Kruppel-Like Transcription Factors
Down-Regulation
Streptozocin
Diabetes Mellitus
Experimental
03 medical and health sciences
Downregulation and upregulation
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Benzhydryl Compounds
Muscle
Skeletal
Transcription factor
Sodium-Glucose Transporter 2 Inhibitors
business.industry
Gene Expression Profiling
Skeletal muscle
Metabolism
medicine.disease
030104 developmental biology
Endocrinology
HEK293 Cells
Hyperglycemia
Proteolysis
biology.protein
business
Popis: Diabetes mellitus is associated with various disorders of the locomotor system including the decline in mass and function of skeletal muscle. The mechanism underlying this association has remained ambiguous, however. We now show that the abundance of the transcription factor KLF15 as well as the expression of genes related to muscle atrophy are increased in skeletal muscle of diabetic model mice, and that mice with muscle-specific KLF15 deficiency are protected from the diabetes-induced decline of skeletal muscle mass. Hyperglycemia was found to upregulate the KLF15 protein in skeletal muscle of diabetic animals, which is achieved via downregulation of the E3 ubiquitin ligase WWP1 and consequent suppression of the ubiquitin-dependent degradation of KLF15. Our results revealed that hyperglycemia, a central disorder in diabetes, promotes muscle atrophy via a WWP1/KLF15 pathway. This pathway may serve as a therapeutic target for decline in skeletal muscle mass accompanied by diabetes mellitus.
Databáze: OpenAIRE
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