{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:12:56Z","timestamp":1792098776762,"version":"4.4.0"},"reference-count":22,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2012,7,18]],"date-time":"2012-07-18T00:00:00Z","timestamp":1342569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,7,18]],"date-time":"2012-07-18T00:00:00Z","timestamp":1342569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron Exp Nephrol"],"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; The mineralocorticoid hormone, aldosterone, has pro-fibrotic properties which can cause kidney damage. The severity of kidney interstitial fibrosis is dependent on the accumulation of fibroblasts, which result largely from local proliferation; however, it is unknown whether aldosterone stimulates kidney fibroblast proliferation. Therefore, we examined the effects of aldosterone on the proliferation of cultured kidney fibroblasts. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Uptake of &lt;sup&gt;3&lt;\/sup&gt;H-thymidine and cell number quantitation were used to determine the proliferative effects of aldosterone on a rat kidney fibroblast cell line (NRK49F cells) and interstitial fibroblasts extracted from mouse kidneys after unilateral ureter obstruction. The role of different mitogenic signalling pathways in aldosterone-induced proliferation was assessed using specific inhibitors of receptors and kinases. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Physiological levels of aldosterone induced a doubling of proliferation of kidney fibroblasts (p &lt; 0.0001), which was inhibited by pre-treatment with the mineralocorticoid receptor antagonist, eplerenone. Aldosterone-induced fibroblast proliferation was dependent upon the kinase activity of growth factor receptors [platelet-derived growth factor receptor (PDGFR) and epidermal growth factor receptor]. Notably, PDGF ligands were not involved in aldosterone-induced PDGFR activation, indicating receptor transactivation. Aldosterone-induced fibroblast proliferation also required signalling via PI3K, JNK and ERK pathways, but not via the transforming growth factor-\u03b2&lt;sub&gt;1&lt;\/sub&gt; receptor. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Aldosterone ligation of the mineralocorticoid receptor in kidney fibroblasts results in rapid activation of growth factor receptors and induction of PI3K\/MAPK signalling, which stimulates proliferation. This suggests that increased levels of aldosterone during disease may promote the severity of kidney fibrosis by inducing fibroblast proliferation.<\/jats:p>","DOI":"10.1159\/000339500","type":"journal-article","created":{"date-parts":[[2012,7,18]],"date-time":"2012-07-18T03:50:28Z","timestamp":1342583428000},"page":"e115-e122","source":"Crossref","is-referenced-by-count":55,"title":["Aldosterone Induces Kidney Fibroblast Proliferation via Activation of Growth Factor Receptors and PI3K\/MAPK Signalling"],"prefix":"10.1159","volume":"120","author":[{"given":"L.L.","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.J.","family":"Nikolic-Paterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.Y.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.H.","family":"Tesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2012,7,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000086472.65806.73"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1093%2Fndt%2Fgfn448"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1210%2Fen.2006-0944"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00017.2008"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1159%2F000225379"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1161%2F01.HYP.0000174593.88899.68"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1093%2Fndt%2F12.1.43"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00480.2006"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1161%2Fhy0302.105295"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1161%2FHYPERTENSIONAHA.107.102640"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159%2F000076405"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00125-009-1399-3"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1161%2F01.HYP.0000175814.18550.c0"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2FS0039-128X%2801%2900183-0"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.90428.2008"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1128%2FMCB.21.19.6387-6394.2001"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1161%2FATVBAHA.108.168021"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1167%2Fiovs.02-0260"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000050415.97942.2F"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M413081200"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1096%2Ffj.04-2370com"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1523-1755.2001.059002579.x"}],"container-title":["Nephron Experimental Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/339500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/339500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T14:29:36Z","timestamp":1745418576000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000339500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,18]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2012,10,1]]},"published-print":{"date-parts":[[2012,10,26]]}},"URL":"https:\/\/doi.org\/10.1159\/000339500","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5463685","asserted-by":"subject"}]},"ISSN":["1660-2129"],"issn-type":[{"value":"1660-2129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,18]]}}}