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 |
Externí odkaz: |