| First Author | Wan Y | Year | 2023 |
| Journal | FASEB J | Volume | 37 |
| Issue | 8 | Pages | e23086 |
| PubMed ID | 37428652 | Mgi Jnum | J:346262 |
| Mgi Id | MGI:7614917 | Doi | 10.1096/fj.202300395RRR |
| Citation | Wan Y, et al. (2023) Cathepsin S deficiency improves muscle mass loss and dysfunction via the modulation of protein metabolism in mice under pathological stress conditions. FASEB J 37(8):e23086 |
| abstractText | Cathepsin S (CTSS) is a widely expressed cysteinyl protease that has garnered attention because of its enzymatic and non-enzymatic functions under inflammatory and metabolic pathological conditions. Here, we examined whether CTSS participates in stress-related skeletal muscle mass loss and dysfunction, focusing on protein metabolic imbalance. Eight-week-old male wildtype (CTSS(+/+) ) and CTSS-knockout (CTSS(-/-) ) mice were randomly assigned to non-stress and variable-stress groups for 2 weeks, and then processed for morphological and biochemical studies. Compared with non-stressed mice, stressed CTSS(+/+) mice showed significant losses of muscle mass, muscle function, and muscle fiber area. In this setting, the stress-induced harmful changes in the levels of oxidative stress-related (gp91(phox) and p22(phox) ,), inflammation-related (SDF-1, CXCR4, IL-1beta, TNF-alpha, MCP-1, ICAM-1, and VCAM-1), mitochondrial biogenesis-related (PPAR-gamma and PGC-1alpha) genes and/or proteins and protein metabolism-related (p-PI3K, p-Akt, p-FoxO3alpha, MuRF-1, and MAFbx1) proteins; and these alterations were rectified by CTSS deletion. Metabolomic analysis revealed that stressed CTSS(-/-) mice exhibited a significant improvement in the levels of glutamine metabolism pathway products. Thus, these findings indicated that CTSS can control chronic stress-related skeletal muscle atrophy and dysfunction by modulating protein metabolic imbalance, and thus CTSS was suggested to be a promising new therapeutic target for chronic stress-related muscular diseases. |
