Myostatin deficiency not only prevents muscle wasting but also improves survival in septic mice
| Autor: | Shingo Yasuhara, Shohei Shinozaki, Shingo Kasamatsu, Masao Kaneki, Masayuki Kobayashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor medicine.medical_specialty Cachexia Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Ubiquitin-Protein Ligases Muscle Proteins Myostatin HMGB1 Sepsis Tripartite Motif Proteins 03 medical and health sciences Mice 0302 clinical medicine Lipocalin-2 Liver Function Tests Physiology (medical) Internal medicine Myokine Medicine Animals Phosphorylation Wasting biology business.industry Liver Diseases Acute kidney injury Acute Kidney Injury medicine.disease musculoskeletal system Survival Analysis Muscle atrophy Muscular Atrophy 030104 developmental biology Endocrinology Cytokine Neutrophil Infiltration 030220 oncology & carcinogenesis biology.protein medicine.symptom business Research Article |
| Zdroj: | Am J Physiol Endocrinol Metab |
| Popis: | Sepsis remains a leading cause of mortality in critically ill patients. Muscle wasting is a major complication of sepsis and negatively affects clinical outcomes. Despite intense investigation for many years, the molecular mechanisms underlying sepsis-related muscle wasting are not fully understood. In addition, a potential role of muscle wasting in disease development of sepsis has not been studied. Myostatin is a myokine that downregulates skeletal muscle mass. We studied the effects of myostatin deficiency on muscle wasting and other clinically relevant outcomes, including mortality and bacterial clearance, in mice. Myostatin deficiency prevented muscle atrophy along with inhibition of increases in muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1 expression and phosphorylation of signal transducer and activator of transcription protein 3 (STAT3; major players of muscle wasting) in septic mice. Moreover, myostatin deficiency improved survival and bacterial clearance of septic mice. Sepsis-induced liver dysfunction, acute kidney injury, and neutrophil infiltration into the liver and kidney were consistently mitigated by myostatin deficiency, as indicated by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase activity in the organs. Myostatin deficiency also inhibited sepsis-induced increases in plasma high-mobility group protein B1 (HMGB1) and macrophage inhibitory cytokine (MIC)-1/growth differentiation factor (GDF)-15 concentrations. These results indicate that myostatin plays an important role not only in muscle wasting but also in other clinically relevant outcomes in septic mice. Furthermore, our data raise the possibility that muscle wasting may not be simply a complication, but myostatin-mediated muscle cachexia and related changes in muscle may actually drive the development of sepsis as well. NEW & NOTEWORTHY Muscle wasting is a major complication of sepsis, but its role in the disease development is not known. Myostatin deficiency improved bacterial clearance and survival and mitigated damage in the liver and kidney in septic mice, which paralleled prevention of muscle wasting. These results raise the possibility that muscle wasting may not simply be a complication of sepsis, but myostatin-mediated cachexic changes may have a role in impaired bacterial clearance and mortality in septic mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|