{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:20:59Z","timestamp":1787318459539,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370542\u53f7"],"award-info":[{"award-number":["82370542\u53f7"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenesis of ulcerative colitis (UC) involves genetic susceptibility and immune dysregulation. However, a more comprehensive understanding of its underlying mechanisms is still required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Weighted correlation network analysis (WGCNA) and Mendelian randomization (MR) were used to investigate the association and causality between lipid metabolism and UC. Hub genes were identified by applying ensemble machine learning (LASSO, SVM, XGBoost) to the merged transcriptomic data, followed by cell-type-specific localization using public single-cell RNA-seq data from UC tissues. Pathophysiological relevance was confirmed in a DSS-induced colitis mouse model. The mechanistic role of the key hub gene was defined through knockdown LPS challenge in colonic epithelial cells, coupled with transcriptomic profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Integrated WGCNA and MR  analyses established a strong association between UC and lipid metabolic pathways, which was experimentally confirmed by marked intracellular lipid accumulation in UC models. Mechanistically, this dysregulation was traced to lysosomal dysfunction, a finding solidified by pharmacological modulation with Rapamycin (enhancer) and Chloroquine (inhibitor), which directly demonstrated that lysosomal activity governs lipid metabolic disturbance. Subsequent machine-learning-based feature selection from lysosome-related genes pinpointed TRIM29 as a central regulator. Functional and transcriptomic analyses together demonstrated that TRIM29 knockdown attenuates UC progression by rescuing the lysosome-lipid metabolism axis, as evidenced by restored lysosomal function, enhanced cytoskeletal transport, improved lipid catabolism, a resolved pro-inflammatory immune profile, and downregulated inflammatory signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies TRIM29 as a master regulator that drives UC progression by disrupting lysosomal function and reprogramming lipid metabolism. Our work delineates the TRIM29-lysosome-lipid metabolism axis, providing a mechanistic rationale for targeting TRIM29 as a promising therapeutic strategy in UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1728932","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:44:23Z","timestamp":1768196663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["TRIM29 drives ulcerative colitis by disrupting lipid metabolism via lysosomal dysfunction: a multi-omics and experimental study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xing-Zhou","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong-Biao","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Dong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Fei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Ping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Guo","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Inflammatory bowel disease: cause and immunobiology","volume":"369","author":"Baumgart","year":"2007","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: current state of the art","volume":"13","author":"de Souza","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/1751-2980.12994","article-title":"Chinese Society of Gastroenterology. 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