{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:40:42Z","timestamp":1785451242832,"version":"3.56.0"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) frequently coexist, exacerbating disease burden. However, the molecular mechanisms underlying the progression from T2DM to T2DM\u2010associated NAFLD remain unclear. This study investigated the regulatory function of FOS\u2010mediated PTGS2 activation in this transition. We integrated bulk RNA\u2010seq data from GEO, single\u2010cell transcriptomic data and transcriptomes from patients with T2DM\u2010associated NAFLD. Differentially expressed genes were identified using the limma package, and T2DM\u2010related gene modules were defined by weighted gene co\u2010expression network analysis. LASSO regression and random forest identified 14 candidate genes, with PTGS2 and FOS prioritised. Single\u2010cell analysis showed increased FOS and PTGS2 expression in monocytes, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and Kupffer cells. Transcription factor prediction and dual\u2010luciferase assays confirmed that FOS directly binds the PTGS2 promoter and drives its transcription. In\u00a0vitro, FOS silencing decreased PTGS2 expression, cytokine secretion and apoptosis under high\u2010glucose and free fatty acid conditions, whereas PTGS2 overexpression exacerbated inflammation and apoptosis independently of FOS expression. These findings demonstrate that FOS transcriptionally activates PTGS2, contributing to hepatic inflammation and apoptosis during the progression from T2DM to NAFLD. PTGS2 may serve as a promising biomarker and therapeutic target for T2DM\u2010associated NAFLD.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71182","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T03:50:42Z","timestamp":1778471442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Bulk and Single\u2010Cell\n                    <scp>RNA<\/scp>\n                    \u2010Seq Analysis Reveals Transcriptional Activation of\n                    <scp>PTGS2<\/scp>\n                    by\n                    <scp>FOS<\/scp>\n                    in Progression From\n                    <scp>T2DM<\/scp>\n                    to\n                    <scp>T2DM<\/scp>\n                    \u2010Associated\n                    <scp>NAFLD<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"given":"Rong","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine for Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leqin","family":"Xu","sequence":"additional","affiliation":[{"name":"Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjing","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Xiamen Hospital of Traditional Chinese Medicine (Xiamen Hospital, Beijing University of Chinese Medicine)  Xiamen 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