{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:51:19Z","timestamp":1791975079601,"version":"4.4.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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","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>\n                      Acute Respiratory Distress Syndrome (ARDS) is characterized by alveolar fibrin deposition, driven by dysregulated hypercoagulation and impaired fibrinolysis. Although alveolar epithelial type II (AEC II) cells contribute to this imbalance by overexpressing Tissue Factor (TF) and Plasminogen Activator Inhibitor-1 (PAI-1), the upstream regulatory mechanisms, particularly at the epitranscriptomic level, remain unclear. The potential role of the N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) RNA demethylase FTO in ARDS pathogenesis is unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we employed lipopolysaccharide (LPS)-induced rat ARDS models and LPS-stimulated AEC II cells as primary experimental systems to investigate the underlying mechanisms. Multi-omics profiling, combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq), was performed. Gain and loss-of-function studies were conducted using lentiviral vectors both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Mechanistic investigations involved MeRIP-qPCR, mRNA stability assays, co-immunoprecipitation (Co-IP), Western blot, immunofluorescence, and pharmacological modulation of the NF-\u03baB pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lungs from ARDS rats showed decreased global levels and increased FTO expression. Knockdown of FTO alleviated lung injury, reduced pulmonary edema, and suppressed the expression of TF and PAI-1, concomitant with inhibition of NF-\u03baB signaling. Integrated multi-omics analysis identified Protein Kinase C Beta (PRKCB), a serine\/threonine kinase known to regulate inflammatory signaling, as a key target of FTO. Mechanistically, FTO-mediated demethylation of PRKCB mRNA reduced its recognition by reader proteins that typically promote mRNA decay, thereby prolonging its half-life and enhancing protein translation. Elevated PRKCB promoted IKK\u03b2 phosphorylation and subsequent NF-\u03baB activation. Rescue experiments confirmed that FTO regulates alveolar hypercoagulation and fibrinolytic inhibition in ARDS via PRKCB-dependent activation of the NF-\u03baB pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study identifies the FTO-PRKCB-NF-\u03baB axis as a novel epitranscriptomic pathway driving alveolar fibrin deposition in ARDS. These findings reveal FTO as a potential therapeutic target for mitigating alveolar hypercoagulation and fibrinolysis inhibition in ARDS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1960313","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:22:07Z","timestamp":1791973327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["FTO-mediated demethylation of PRKCB mRNA activates NF-\u03baB to trigger alveolar fibrin deposition in ARDS"],"prefix":"10.3389","volume":"17","author":[{"given":"Xianjun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]},{"name":"Department of Respiratory and Critical Care Medicine, Wuhan No. 1 Hospital","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Anorectal Surgery, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Chen","sequence":"additional","affiliation":[{"name":"Houshan Township Health Center","place":["Zunyi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00439-6","article-title":"Acute respiratory distress syndrome","volume":"398","author":"Meyer","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201610-2156SO","article-title":"Fifty years of research in ARDS. 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