{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:14:03Z","timestamp":1768011243339,"version":"3.49.0"},"reference-count":25,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p> Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric tubular injury; however, whether dysregulation of the renin-angiotensin system (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous Ren2 rats, characterized by renal damage through excessive RAS activation. We also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats received a nonhypotensive dose of candesartan (0.05 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> sc) or the p38 inhibitor SB-239063 (15 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> sc) for 4 wk; untreated Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein expression were determined by quantitative PCR and immunohistochemistry, respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1 was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting enzyme inhibition (ramipril, 1 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> in drinking water for 4 wk). Untreated Ren2 rats showed a &gt;20-fold increase in renal Kim-1 mRNA (expressed as Kim-1-to-GAPDH ratio): 75.5 \u00b1 43.6 vs. 3.1 \u00b1 1.0 in SD rats ( P &lt; 0.01). Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 \u00b1 1.5 ( P &lt; 0.01) and 9.8 \u00b1 4.2 ( P &lt; 0.05), respectively. Kim-1 protein expression in damaged tubules paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin, \u03b1-smooth muscle actin, and collagen III expression and with tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38 also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 \u00b1 70 vs. 27 \u00b1 2 pg\/ml, P &lt; 0.01) rats and abolished in Ren2 rats treated with ramipril (33 \u00b1 5 pg\/ml, P &lt; 0.01). Kim-1 is associated with development of RAS-mediated renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase inhibition reduced Kim-1 in the homozygous Ren2 model. <\/jats:p>","DOI":"10.1152\/ajprenal.00180.2006","type":"journal-article","created":{"date-parts":[[2006,8,8]],"date-time":"2006-08-08T23:58:36Z","timestamp":1155081516000},"page":"F313-F320","source":"Crossref","is-referenced-by-count":55,"title":["Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase"],"prefix":"10.1152","volume":"292","author":[{"given":"Martin H.","family":"de Borst","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjan M.","family":"van Timmeren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishal S.","family":"Vaidya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf A.","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario B. 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