{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:22:25Z","timestamp":1781835745666,"version":"3.54.5"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"crossref","award":["R01DA042524,R01DA052845,R01DA050169,P30AI161943,P51OD011104,P51OD111033"],"award-info":[{"award-number":["R01DA042524,R01DA052845,R01DA050169,P30AI161943,P51OD011104,P51OD111033"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,10]]},"abstract":"<jats:p>\n                    Intestinal epithelial barrier dysfunction, a hallmark of HIV\/SIV infection, persists despite viral suppression by combination antiretroviral therapy (cART). Emerging evidence suggests a critical role for long noncoding RNAs (lncRNAs) in maintaining epithelial homeostasis. We simultaneously profiled lncRNA\/mRNA expression exclusively in colonic epithelium (CE) of SIV-infected rhesus macaques (RMs) administered vehicle (VEH) or \u0394-9-tetrahydrocannabinol (THC). Relative to controls, fewer lncRNAs were up- or downregulated in CE of THC\/SIV compared with VEH\/SIV RMs. Importantly, reciprocal expression of the natural antisense lncRNA\n                    <jats:italic>MMP25-AS1<\/jats:italic>\n                    (up 2.3-fold) and its associated protein-coding gene\n                    <jats:italic>MMP25<\/jats:italic>\n                    (attracts neutrophils by inactivating alpha-1 anti-trypsin\/SERPINA1) (down 2.2-fold) was detected in CE of THC\/SIV RMs. Computational analysis verified 2 perfectly matched complementary regions and an energetically stable (normalized binding free energy = \u20130.2626)\n                    <jats:italic>MMP25-AS1\/MMP25<\/jats:italic>\n                    duplex structure.\n                    <jats:italic>MMP25-AS1<\/jats:italic>\n                    overexpression blocked IFN-\u03b3\u2013induced MMP25 mRNA and protein expression in vitro. Elevated MMP25 protein expression in CE of VEH\/SIV but not THC\/SIV RMs was associated with increased infiltration by myeloperoxidase\/CD11b\n                    <jats:sup>++<\/jats:sup>\n                    neutrophils (transendothelial migration) and epithelial CD47 (transepithelial migration) expression. Interestingly, THC administered in combination with cART increased\n                    <jats:italic>MMP25-AS1<\/jats:italic>\n                    and reduced MMP25 mRNA\/protein expression in jejunal epithelium of SIV-infected RMs. Our findings demonstrate that\n                    <jats:italic>MMP25-AS1<\/jats:italic>\n                    is a potentially unique epigenetic regulator of\n                    <jats:italic>MMP25<\/jats:italic>\n                    and that low-dose THC can reduce neutrophil infiltration and intestinal epithelial injury potentially by downregulating\n                    <jats:italic>MMP25<\/jats:italic>\n                    expression through modulation of\n                    <jats:italic>MMP25-AS1<\/jats:italic>\n                    .\n                  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