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Title: NF-kappa B and GATA-Binding Factor 6 Repress Transcription of Caveolins in Bladder Smooth Muscle Hypertrophy
Authors: THANGAVEL, ChellappagounderGOMES, Cristiano M.ZDERIC, Stephen A.JAVED, ElhamADDYA, SankarSINGH, JagmohanDAS, SreyaBIRBE, RuthDEN, Robert B.RATTAN, SatishDESHPANDE, Deepak A.PENN, Raymond B.CHACKO, SamuelBOOPATHI, Ettickan
Citation: AMERICAN JOURNAL OF PATHOLOGY, v.189, n.4, p.847-867, 2019
Abstract: Caveolins (CAVs) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV protein expression is associated with impaired contraction in obstruction-induced bladder smooth muscle (BSM) hypertrophy. In this study, microarray analysis of bladder RNA revealed down-regulation of CAV1, CAV2, and CAV3 gene transcription in BSM from models of obstructive bladder disease in mice and humans. We identified and characterized regulatory regions responsible for CAV1, CAV2, and CAV3 gene expression in mice with obstruction-induced BSM hypertrophy, and in men with benign prostatic hyperplasia. DNA affinity chromatography and chromatin immunoprecipitation assays revealed a greater increase in binding of GATA-binding factor 6 (GATA-6) and NE-KB to their cognate binding motifs on CAV1, CAV2, and CAV3 promoters in obstructed BSM relative to that observed in control BSM. Knockout of NE-KB subunits, shRNA-mediated knockdown of GATA-6, or pharmacologic inhibition of GATA-6 and NE-KB in BSM increased CAV1, CAV2, and CAV3 transcription and promoter activity. Conversely, overexpression of GATA-6 decreased CAV2 and CAV3 transcription and promoter activity. Collectively, these data provide new insight into the mechanisms by which CAV gene expression is repressed in hypertrophied BSM in obstructive bladder disease.
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Artigos e Materiais de Revistas Científicas - HC/IOT
Instituto de Ortopedia e Traumatologia - HC/IOT

Artigos e Materiais de Revistas Científicas - LIM/55
LIM/55 - Laboratório de Urologia

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