Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human Beings

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP BOOPATHI, Ettickan
GOMES, Cristiano Mendes FMUSP-HC
JOHN, Mary
SRINIVASAN, Vittala Gopal
KATHURIA, Hasmeena
ZDERIC, Stephen A.
WEIN, Alan J.
CHACKO, Samuel 2011
dc.identifier.citation AMERICAN JOURNAL OF PATHOLOGY, v.178, n.5, p.2236-2251, 2011
dc.identifier.issn 0002-9440
dc.description.abstract Hypertrophy occurs in urinary bladder wall smooth muscle (BSM) in men with partial bladder outlet obstruction (PBOO) caused by benign prostatic hyperplasia (BPH) and in animal models of PBOO. Hypertrophied BSM from the rabbit model exhibits down-regulation of caveolin-1, a structural and functional protein of caveolae that function as signaling platforms to mediate interaction between receptor proteins and adaptor and effector molecules to regulate signal generation, amplification, and diversification. Caveolin-1 expression is diminished in PBOO-induced BSM hypertrophy in mice and in men with BPH. The proximal promoter of the human and mouse caveolin-1 (CAV1) gene was characterized, and it was observed that the transcription factor GATA-6 binds this promoter, causing reduced expression of caveolin-1. Furthermore, caveolin-1 expression levels inversely correlate with the abundance of GATA-6 in BSM hypertrophy in mice and human beings. Silencing of GATA6 gene expression up-regulates caveolin-1 expression, whereas overexpression of GATA-6 protein sustains the transcriptional repression of caveolin-1 in bladder smooth muscle cells. Together, these data suggest that GATA-6 acts as a transcriptional repressor of CAV1 gene expression in PBOO-induced BSM hypertrophy in men and mice. GATA-6-induced transcriptional repression represents a new regulatory mechanism of CAV1 gene expression in pathologic BSM, and may serve as a target for new therapy for BPH-induced bladder dysfunction in aging men. (Am J Pathol 2011, 178:2236-2251; DOI 10.1016/j.ajpath.2011.01.038)
dc.description.sponsorship · George O'Brien Urology Research Center [P50 DK052620]
dc.language.iso eng
dc.relation.ispartof American Journal of Pathology
dc.rights restrictedAccess
dc.subject.other urinary-tract function; outlet obstruction; cell-lines; continence-society; binding-proteins; ets proteins; lipid rafts; map kinase; in-vivo; differentiation
dc.title Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human Beings
dc.type article
dc.rights.holder Copyright ELSEVIER SCIENCE INC LIM/55
dc.identifier.doi 10.1016/j.ajpath.2011.01.038
dc.identifier.pmid 21514437
dc.type.category original article
dc.type.version publishedVersion GOMES, Cristiano Mendes:HC:IOT · KATHURIA, Hasmeena:Boston Univ, Sch Med, Boston, MA 02118 USA
· ZDERIC, Stephen A.:Childrens Hosp Philadelphia, Dept Urol, Philadelphia, PA 19104 USA
· CHACKO, Samuel:Univ Penn, Glenolden Res Lab, Div Urol, Glenolden, PA 19036 USA; Univ Penn, Dept Pathobiol, Glenolden, PA 19036 USA WOS:000298306800030 2-s2.0-79959256001 NEW YORK USA
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dc.description.index MEDLINE
hcfmusp.citation.scopus 24
hcfmusp.citation.wos 23 Brasil Estados Unidos

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