{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:41:10Z","timestamp":1792590070174,"version":"4.5.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>\n                    Aldosterone (Aldo) can be a profibrotic factor in cardiovascular and renal tissues. This study tests the hypothesis that prolonged Aldo exposure is able to directly induce fibrotic changes in the kidney of a normal nonhypertensive animal. Immortalized rat proximal tubule cells (IRPTC) containing 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD1) but no mineralocorticoid receptors (MR) and mouse inner medullary collecting duct cells (IMCD) containing 11\u03b2-HSD2 and MR were examined. IRPTC exposed to Aldo or corticosterone (10 nM) for 48 h demonstrated no change in collagen production as assessed by Sirius red staining. In contrast, IMCD treated with Aldo exhibited a marked increase in the expression of collagen, fibronectin, and connective tissue growth factor (CTGF), whereas corticosterone alone had no effect. The Aldo-induced overexperession of collagen, fibronectin, and CTGF was substantially attenuated by the MR antagonist RU-318 and by the 11\u03b2-HSD end product 11-dehydrocorticosterone, but not by the glucocorticoid receptor antagonist RU-486. In vivo, early fibrotic changes with elevated collagen, fibronectin, and CTGF expression were observed in kidneys isolated from normotensive adrenalectomized mice receiving a continuous infusion of Aldo (8 \u03bcg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) for 1 wk. These changes were not present in corticosterone-treated mice. Aldo-induced changes were attenuated in adrenally intact mice and in mice treated with RU-318 or 11-dehydrocorticosterone. Thus, extended Aldo exposure produces fibrotic changes in cells containing MR and in normal kidneys. MR antagonists and the end products of 11\u03b2-HSD attenuate these fibrogenic effects.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00532.2009","type":"journal-article","created":{"date-parts":[[2010,3,3]],"date-time":"2010-03-03T20:51:05Z","timestamp":1267649465000},"page":"F1178-F1187","source":"Crossref","is-referenced-by-count":30,"title":["Direct fibrogenic effects of aldosterone on normotensive kidney: an effect modified by 11\u03b2-HSD activity"],"prefix":"10.1152","volume":"298","author":[{"given":"Andrew S.","family":"Brem","sequence":"first","affiliation":[{"name":"Division of Kidney Diseases and Hypertension, Rhode Island Hospital,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Miriam Hospital, Brown Medical School, Providence, Rhode 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