{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:39:54Z","timestamp":1787013594104,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbiology and Immunology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Chronic kidney disease (CKD)\u2010related sarcopenia is a debilitating complication characterized by progressive skeletal muscle loss, primarily driven by oxidative stress and inflammation. However, the molecular mechanisms underlying this condition are still not fully clarified. This study aimed to investigate the role of N6\u2010methyladenosine (m\u2076A) Methyltransferase\u2010Like 3 (METTL3) in mediating oxidative stress and inflammation through the TLR4\/NF\u2010\u03baB signaling pathway in the context of CKD\u2010associated muscle atrophy. C2C12 myoblasts were treated with Indoxyl Sulfate (IS) to mimic the uremic environment of CKD.METTL3 expression was silenced via shRNA, and lipopolysaccharide (LPS) was used to activate TLR4\/NF\u2010\u03baB signaling. Proinflammatory cytokines, oxidative stress levels, and Myogenic differentiation markers were measured using qRT\u2010PCR, Western blot analysis, enzyme\u2010linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) assays. The interaction between METTL3 and Toll\u2010like receptor 4(TLR4) mRNA was confirmed by methylated RNA immunoprecipitation (MeRIP). A CKD rat model was established via 5\/6 nephrectomy, followed by in vivo METTL3 silencing using AAV\u2010shRNA to assess muscle atrophy and renal function. METTL3 was significantly upregulated in IS\u2010treated myoblasts and CKD rat muscle tissue. Knockdown of METTL3 restored myogenic differentiation, reduced ROS and malondialdehyde levels, increased glutathione (GSH) content, and suppressed the expression of TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2. MeRIP analysis confirmed m\u2076A modification of TLR4 mRNA mediated by METTL3, which enhanced TLR4 expression and downstream NF\u2010\u03baB activation. METTL3 silencing in CKD rats improved muscle histology, reduced systemic inflammation, and partially restored renal function. METTL3 promotes oxidative stress, inflammation, and skeletal muscle atrophy in CKD\u2010associated sarcopenia by enhancing TLR4\/NF\u2010\u03baB signaling via m\u2076A modification. These findings identify METTL3 as a potential therapeutic target for ameliorating sarcopenia in CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1348-0421.70014","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T07:15:59Z","timestamp":1760339759000},"page":"608-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["METTL3 Promotes Oxidative Stress and Inflammation in Myoblasts During Chronic Kidney Disease Related Sarcopenia Through the TLR4 NF\u2010\u03baB Pathway"],"prefix":"10.1111","volume":"69","author":[{"given":"Qiong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology The First People's Hospital of Chenzhou Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First People's Hospital of Chenzhou Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghai","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First People's Hospital of Chenzhou Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First People's Hospital of Chenzhou Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5084-8489","authenticated-orcid":false,"given":"Yi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery The First People's Hospital of Chenzhou Chenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_14_2_1","article-title":"Sarcopenia, Sarcopenic Obesity, and Frailty in Individuals With 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