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The present study was designed to test the hypothesis that COX\u20102 activity attenuates fibrosis and preserves microvasculature in injured kidney. The murine unilateral ureteral\u2010obstruction (UUO) model of kidney fibrosis was employed and compared with human nephrectomy tissue with and without chronic hydronephrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fibrosis and angiogenic markers were quantified in kidney tissue from wild\u2010type and COX\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice subjected to UUO for 7\u2009days and in human kidney tissue. COX\u2010enzymes, prostaglandin (PG) synthases, PG receptors, PGE<jats:sub>2<\/jats:sub>, and thromboxane were determined in human tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>COX\u20102 immunosignal was observed in interstitial fibroblasts at baseline and after UUO. Fibronectin, collagen I, III, alpha\u2010smooth muscle actin, and fibroblast specific protein\u20101 mRNAs increased significantly more after UUO in COX\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> vs wild\u2010type mice. In vitro, fibroblasts from COX\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> kidneys showed higher matrix synthesis. Compared to control, human hydronephrotic kidneys showed (i) fibrosis, (ii) no significant changes in COX\u20102, COX\u20101, PGE<jats:sub>2<\/jats:sub>\u2010, and prostacyclin synthases, and prostacyclin and thromboxane receptor mRNAs, (iii) increased mRNA and protein of PGE<jats:sub>2<\/jats:sub>\u2010EP<jats:sub>2<\/jats:sub> receptor level but unchanged PGE<jats:sub>2<\/jats:sub> tissue concentration, and (iv) two\u2010 to threefold increased thromboxane synthase mRNA and protein levels, and increased thromboxane B<jats:sub>2<\/jats:sub> tissue concentration in cortex and outer medulla.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>COX\u20102 protects in the early phase against obstruction\u2010induced fibrosis and maintains angiogenic factors. Increased PGE<jats:sub>2<\/jats:sub>\u2010EP<jats:sub>2<\/jats:sub> receptor in obstructed human and murine kidneys could contribute to protection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13828","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T08:09:02Z","timestamp":1652256542000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased <scp>COX<\/scp>\u20102 after ureter obstruction attenuates fibrosis and is associated with <scp>EP<sub>2<\/sub><\/scp> receptor upregulation in mouse and human kidney"],"prefix":"10.1111","volume":"235","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-4272","authenticated-orcid":false,"given":"Signe S.","family":"Tofteng","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Renal Research, Institute of Molecular Medicine University of Southern Denmark  Odense 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