{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:52:10Z","timestamp":1778946730674,"version":"3.51.4"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006143","name":"Department of Science and Technology, Government of Kerala","doi-asserted-by":"publisher","award":["DST\/NM\/NT\/2019-191"],"award-info":[{"award-number":["DST\/NM\/NT\/2019-191"]}],"id":[{"id":"10.13039\/501100006143","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Dilated and dysfunctional gut lymphatic vessels (LVs) have been reported in experimental cirrhosis. Here, we studied LVs in duodenal (D2)-biopsies of liver cirrhosis patients and investigated the prognostic role of a LV marker, podoplanin (PDPN), in predicting the mortality of patients with cirrhosis. A prospective, single-center cohort study was performed in liver cirrhosis patients (<jats:italic>n<\/jats:italic> = 31) and matched healthy controls (<jats:italic>n<\/jats:italic> = 9). D2-biopsies were obtained during endoscopy procedure, immunostained with PDPN, and scored based on 1) intensity and 2) density of positively-stained LVs per high power field. Gut and systemic inflammation were estimated by quantifying duodenal CD3<jats:sup>+<\/jats:sup> intraepithelial lymphocytes (IELs), CD68<jats:sup>+<\/jats:sup> macrophages, and serum TNF-\u03b1 and IL-6 levels, respectively. Gut permeability and inflammation as assessed by quantifying gene expression of <jats:italic>TJP1<\/jats:italic>, <jats:italic>OCLN, TNF-\u03b1,<\/jats:italic> and <jats:italic>IL-6<\/jats:italic> in D2-biopsies. Gene expression of LV markers, <jats:italic>PDPN<\/jats:italic> (8-fold), and <jats:italic>LYVE1<\/jats:italic> (3-fold) was enhanced in D2-biopsies of cirrhosis patients compared to control (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001). The mean PDPN score in decompensated cirrhosis patients (6.91 \u00b1 1.26, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) was significantly increased as compared to those with compensated (3.25 \u00b1 1.60). PDPN score positively and significantly correlated with the number of IELs (r = 0.33), serum TNF-\u03b1 (r = 0.35), and IL-6 (r = 0.48) levels, while inversely correlated with <jats:italic>TJP1<\/jats:italic> expression (r = -0.46, <jats:italic>p<\/jats:italic> &amp;lt; 0.05 each). In Cox regression, the PDPN score was a significant and independent 3-month-mortality predictor in patients (HR: 5.61; 1.08-29.109; <jats:italic>p<\/jats:italic> = 0.04). The area under the curve for the PDPN score was 84.2, and cutoff value for predicting mortality was \u22656.5 with 100% sensitivity and 75% specificity. Collectively, dilated LVs with high PDPN expression in D2-biopsies is a characteristic feature of patients with decompensated cirrhosis. PDPN score correlates with enhanced gut and systemic inflammation and also associates with 3-month mortality in cirrhosis.<\/jats:p>","DOI":"10.3389\/fphys.2023.1045983","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T04:47:15Z","timestamp":1684990035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Podoplanin-positive dilated lymphatic vessels in duodenum associates with three-month mortality in patients with cirrhosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Pinky","family":"Juneja","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aarti","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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