{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:27Z","timestamp":1789106847130,"version":"build-2803163510"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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. Pharmacol."],"abstract":"<jats:p>\n                    15-Deoxy-\u039412,14-prostaglandin J\n                    <jats:sub>2<\/jats:sub>\n                    (15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    ), an endogenous cyclooxygenase-derived lipid mediator and natural ligand of peroxisome proliferator-activated receptor gamma (PPAR\u03b3), plays important roles in inflammatory regulation and renal pathophysiology. However, the effect of 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    on cyclooxygenase-2 (COX-2) expression in mesangial cells and the involvement of PPAR\u03b3 in this process remain unclear. In this study, we investigated the regulation of COX-2 expression and prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) production by 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    in primary cultured mouse mesangial cells and determined the role of PPAR\u03b3 using pharmacological and genetic approaches. Treatment with 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    significantly increased COX-2 mRNA and protein expression, accompanied by a marked elevation of PGE\n                    <jats:sub>2<\/jats:sub>\n                    production. Pharmacological inhibition of PPAR\u03b3 using the selective antagonist GW9662 did not affect 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    -induced COX-2 expression or PGE2 production. Similarly, overexpression of dominant-negative PPAR\u03b3, siRNA-mediated knockdown, and Cre-mediated genetic deletion of PPAR\u03b3 failed to attenuate the induction of COX-2 by 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    . Functional reporter assays confirmed effective modulation of PPAR\u03b3 transcriptional activity under these conditions, indicating that the lack of effect was not due to insufficient inhibition. These findings demonstrate that 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    induces COX-2 expression and enhances PGE\n                    <jats:sub>2<\/jats:sub>\n                    production in mouse mesangial cells via a mechanism independent of PPAR\u03b3. This PPAR\u03b3-independent action suggests alternative signaling pathways through which endogenous lipid mediators regulate inflammatory responses in the kidney. Our results provide new insight into the complex role of prostaglandin metabolites in renal inflammatory signaling and highlight the importance of receptor-independent actions of electrophilic lipid mediators.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1924049","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:29:29Z","timestamp":1789104569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["15- Deoxy-\u039412,14-prostaglandin J2 upregulates COX-2 expression and PGE2 in mouse mesangial cells through a mechanism independent of PPAR\u03b3"],"prefix":"10.3389","volume":"17","author":[{"given":"Bo","family":"Yu","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqi","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyan","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghao","family":"Rong","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangrui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Shanghai University of Medicine and Health Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41581-020-00339-6","article-title":"Nuclear receptors in podocyte biology and glomerular disease","volume":"17","author":"Agrawal","year":"2021","journal-title":"Nat. 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