{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:41:35Z","timestamp":1777502495081,"version":"3.51.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The  mechanisms by which persistent proteinuria induces  interstitial inflammation and fibrosis are not well known,  although nuclear factor-\u03baB (NF-\u03baB), which regulates the  transcription of many genes involved in renal injury, could be  implicated. In rats with intense proteinuria, we studied the renal  activation of NF-\u03baB as well as the potential involvement of the  vasoactive hormones angiotensin II (Ang II) and  endothelin-1 (ET-1). Uninephrectomized Wistar-Kyoto rats receiving 1  g\/d of BSA had proteinuria but no renal morphological lesions at day 1.  By contrast, tubular atrophy and\/or dilation and mononuclear cell  infiltration were observed after 8 or 28 days of BSA administration,  coinciding with maximal proteinuria. In relation to control  uninephrectomized rats, the renal cortex of nephritic rats showed an  increment in the activation of NF-\u03baB at all time periods studied. By  in situ Southwestern histochemistry, NF-\u03baB activity was mainly  localized in proximal tubules, interstitial mononuclear  cells, and, to a lesser extent, the glomeruli. The administration of  the ACE inhibitor quinapril plus the  ET\n            <jats:sub>A<\/jats:sub>\n            \/ET\n            <jats:sub>B<\/jats:sub>\n            receptor  antagonist bosentan during 28 days to BSA-overloaded  animals diminished proteinuria, renal lesions, and NF-\u03baB activity  more markedly than single drugs. Cultured tubular epithelial cells  exposed to BSA revealed an intense NF-\u03baB activation in a time- and  dose-dependent manner. Incubation of cells with receptor  antagonists of Ang II (AT\n            <jats:sub>1<\/jats:sub>\n            :  losartan and AT\n            <jats:sub>2<\/jats:sub>\n            : PD-123,319) or ET-1  (ET\n            <jats:sub>A<\/jats:sub>\n            : BQ123 and ET\n            <jats:sub>B<\/jats:sub>\n            :  IRL1038) inhibited significantly the BSA-induced NF-\u03baB activity  (90%, 75%, 90%, and 60% of inhibition versus basal, respectively).  Our results show that overload proteinuria causes NF-\u03baB activation in  tubular epithelial cells both in vivo and in vitro. The vasoactive  peptides Ang II and ET-1 appear to be implicated in this effect. The  results reveal a novel mechanism of perpetuation of renal damage  induced by persistent proteinuria.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.37.4.1171","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"1171-1178","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":123,"title":["Activation of NF-\u03baB in Tubular Epithelial Cells of Rats With Intense Proteinuria"],"prefix":"10.1161","volume":"37","author":[{"given":"Dulcenombre","family":"Go\u0301mez-Garre","sequence":"first","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Largo","sequence":"additional","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Tejera","sequence":"additional","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose\u0301","family":"Fortes","sequence":"additional","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fe\u0301lix","family":"Manzarbeitia","sequence":"additional","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesu\u0301s","family":"Egido","sequence":"additional","affiliation":[{"name":"From the Renal and Vascular Research Laboratory (D.G.-G., R.L., N.T.,  J.E.), Department of Pathology (J.F., F.M.), Fundacio\u0301n Jime\u0301nez  Di\u0301az, Universidad Auto\u0301noma, Madrid, Spain."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"1448","volume":"339","year":"1998","unstructured":"Remuzzi G, Bertani T. 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