{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:16:46Z","timestamp":1784956606285,"version":"3.55.0"},"reference-count":93,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marshall University Joan C. Edwards School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH (the PGE2 degradation enzyme), has been shown to increase in vivo regeneration of liver parenchyma, ameliorating oxidative stress and inflammation. We hypothesized that SW033291 abrogates MASH progression by inducing a paucity of the initial apoptotic switch and restoring physiological collagen\u2019s microenvironment. Methods. The expression levels of the cell metabolic proteins FOXO1, mTOR, and SIRT7 were determined in a diet-induced MASH-mouse model at 16, 20, and 24 weeks. Non-targeted metabolomics in mouse plasma were measured by LC-MS\/MS. Liver morphology and apoptotic activity were quantified by the NAS score and TUNEL assay, respectively. Statistical analyses between groups (NMC, HFD, and SW033291) were determined by ANOVA, t-test\/Tukey\u2019s post hoc test using GraphPad Prism. Metabolomics data were analyzed using R-lab. Results. The treated group showed significant decreases in total body fat, cellular oxidative stress, and inflammation and an increase in total lean mass with improved insulin resistance and favorable modulation of metabolic protein expressions (p &lt; 0.05). SW033291 significantly decreased GS:SG, citric acid, and corticosterone, NAS scores (9.4 \u00b1 0.2 vs. 6.2 \u00b1 0.1, p &lt; 0.05), liver fibrosis scores (1.3 \u00b1 0.5 vs. 0.25 \u00b1 0.1, p &lt; 0.05), and apoptotic activity (43.9 \u00b1 4.6 vs. 0.38 \u00b1 0.1%, p &lt; 0.05) compared with controls at 24W. Conclusions. The inhibition of 15-PGDH appears to normalize the metabolic and morphological disturbances during MASH progression with a paucity of the initial apoptotic switch, restoring normal collagen architecture. SW033291 warrants further investigation for its translation.<\/jats:p>","DOI":"10.3390\/cells14130987","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["INHIBITION OF THE PROSTAGLANDIN-DEGRADING ENZYME 15-PGDH AMELIORATES MASH-ASSOCIATED APOPTOSIS AND FIBROSIS IN MICE"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-7984","authenticated-orcid":false,"given":"Utibe-Abasi S.","family":"Udoh","sequence":"first","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew Steven","family":"Schade","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Sanabria","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep Kumar","family":"Rajan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheal","family":"Andryka","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Gorka","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine V.","family":"Pierre","sequence":"additional","affiliation":[{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7114-2327","authenticated-orcid":false,"given":"Juan","family":"Sanabria","sequence":"additional","affiliation":[{"name":"Department of Surgery, Marshall University Joan Edwards School of Medicine, Huntington, WV 25701, USA"},{"name":"Marshall Institute for Interdisciplinary Research (MIIR), Marshall University, Huntington, WV 25701, USA"},{"name":"Department of Nutrition and Metabolomic Core Facility, School of Medicine, Case Western Reserve University, Cleveland, OH 44100, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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