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The molecular mechanism underlying denervation-induced muscle atrophy is complex and incompletely understood. Our previous results suggested that inflammation may play an important role in the early stages of muscle atrophy. Celecoxib is reported to exert anti-inflammatory effects. Here, we explored the effect of celecoxib on denervation-induced muscle atrophy and sought to identify the mechanism involved. We found that celecoxib treatment significantly increased the wet weight ratio and CSA of the tibialisanteriormuscle. Additionally, celecoxib downregulated the levels of COX-2, inflammatory factors and reduced inflammatory cell infiltration. GO and KEGG pathway enrichment analysis indicated that after 3 days of celecoxib treatment in vivo, the differentially expressed genes (DEGs) were mainly associated with the regulation of immune responses related to complement activation; after 14 days, the DEGs were mainly involved in the regulation of oxidative stress and inflammation-related responses. Celecoxib administration reduced the levels of ROS and oxidative stress-related proteins. Furthermore, we found that celecoxib treatment inhibited the denervation-induced up-regulation of the ubiquitin-proteasome and autophagy-lysosomal systems related proteins; decreased mitophagy in target muscles; and increased levels of MHC. Finally, celecoxib also attenuated microvascular damage in denervated skeletal muscle. Combined, our findings demonstrated that celecoxib inhibits inflammation and oxidative stress in denervated skeletal muscle, thereby suppressing mitophagy and proteolysis, improving blood flow in target muscles, and, ultimately, alleviating denervation-induced muscle atrophy. Our results confirmed that inflammatory responses play a key role in denervation-induced muscle atrophy and highlight a novel strategy for the prevention and treatment of this condition., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

[Display omitted] Chronic kidney disease (CKD) is a high-risk chronic catabolic disease due to its high morbidity and mortality. CKD is accompanied by many complications, leading to a poor quality of life, and serious complications may even threaten the life of CKD patients. Muscle atrophy is a common complication of CKD. Muscle atrophy and sarcopenia in CKD patients have complex pathways that are related to multiple mechanisms and related factors. This review not only discusses the mechanisms by which inflammation, oxidative stress, mitochondrial dysfunction promote CKD-induced muscle atrophy but also explores other CKD-related complications, such as metabolic acidosis, vitamin D deficiency, anorexia, and excess angiotensin II, as well as other related factors that play a role in CKD muscle atrophy, such as insulin resistance, hormones, hemodialysis, uremic toxins, intestinal flora imbalance, and miRNA. We highlight potential treatments and drugs that can effectively treat CKD-induced muscle atrophy in terms of complication treatment, nutritional supplementation, physical exercise, and drug intervention, thereby helping to improve the prognosis and quality of life of CKD patients. [ABSTRACT FROM AUTHOR]