Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/2398
Title: GATA-6 and NF-kappa B Activate CPI-17 Gene Transcription and Regulate Ca2+ Sensitization of Smooth Muscle Contraction
Authors: BOOPATHI, EttickanHYPOLITE, Joseph A.ZDERIC, Stephen A.GOMES, Cristiano MendesMALKOWICZ, BruceLIOU, Hsiou-ChiWEIN, Alan J.CHACKO, Samuel
Citation: MOLECULAR AND CELLULAR BIOLOGY, v.33, n.5, p.1085-1102, 2013
Abstract: Protein kinase C (PKC)-potentiated inhibitory protein of 17 kDa (CPI-17) inhibits myosin light chain phosphatase, altering the levels of myosin light chain phosphorylation and Ca2+ sensitivity in smooth muscle. In this study, we characterized the CPI-17 promoter and identified binding sites for GATA-6 and nuclear factor kappa B (NF-kappa B). GATA-6 and NF-kappa B upregulated CPI-17 expression in cultured human and mouse bladder smooth muscle (BSM) cells in an additive manner. CPI-17 expression was decreased upon GATA-6 silencing in cultured BSM cells and in BSM from NF-kappa B knockout (KO) mice. Moreover, force maintenance by BSM strips from KO mice was decreased compared with the force maintenance of BSM strips from wild-type mice. GATA-6 and NF-kappa B overexpression was associated with CPI-17 overexpression in BSM from men with benign prostatic hyperplasia (BPH)-induced bladder hypertrophy and in a mouse model of bladder outlet obstruction. Thus, aberrant expression of NF-kappa B and GATA-6 deregulates CPI-17 expression and the contractile function of smooth muscle. Our data provide insight into how GATA-6 and NF-kappa B mediate CPI-17 transcription, PKC-mediated signaling, and BSM remodeling associated with lower urinary tract symptoms in patients with BPH.
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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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