23 β-CATENIN SIGNALING CONTRIBUTES TO PDGF-ELICITED BLADDER SMOOTH MUSCLE CELL CONTRACTION THROUGH UPREGULATION OF CX43 EXPRESSION

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201223 β-CATENIN SIGNALING CONTRIBUTES TO PDGF-ELICITED BLADDER SMOOTH MUSCLE CELL CONTRACTION THROUGH UPREGULATION OF CX43 EXPRESSION Kai Li, Jian Yao, Norifumi Sawada, Tatsuya Miyamoto, Masanori Kitamura, and Masayuki Takeda Kai LiKai Li Chuo City, Yamanashi, Japan More articles by this author , Jian YaoJian Yao Chuo, Yamanashi, Japan More articles by this author , Norifumi SawadaNorifumi Sawada Chuo, Yamanashi, Japan More articles by this author , Tatsuya MiyamotoTatsuya Miyamoto Chuo, Yamanashi, Japan More articles by this author , Masanori KitamuraMasanori Kitamura Chuo, Yamanashi, Japan More articles by this author , and Masayuki TakedaMasayuki Takeda Chuo, Yamanashi, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.066AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has been suggested that an elevated number of gap junctions (GJs) may contribute to bladder overactivity. However, the factors and mechanisms involved in the regulation of GJs in the bladder have not been well established. Here we examined whether and how platelet derived growth factor (PDGF) regulates connexin43 (Cx43) in bladder smooth muscle cells (BSMCs). METHODS Cultured rat BSMCs were treated with various growth factors in the presence or absence of agents that interfere with phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) and β-catenin signaling pathways. Cx43 expression was examined by Western blot, Northern blot, and immunochemistry. Functional GJs were evaluated by scrape-loading dye transfer assay. BSMC contraction was measured by collagen gel contraction. RESULTS 1) PDGF induced a PI3K- and MAPK-dependent accumulation of nuclear β-catenin. This was followed by an elevated Cx43 expression (Fig. A). 2) Downregulation of β-catenin with specific siRNA abolished (Fig. B - D), whereas stimulation of β-catenin through inhibition of glycogen synthase kinase (GSK) mimicked the Cx43-elevating effect of PDGF. 3) Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) also induced Cx43 expression. Their effects were potentiated by PDGF. 4) Inhibition of GJs attenuated PDGF-induced BSMC contraction. Consistently, fibroblasts from Cx43 knockout (Cx43−/−) mouse displayed a much weaker contractile response to PDGF than cells from Cx43-wild (Cx43+/+) littermates (Fig. E). CONCLUSIONS PDGF induces Cx43 expression and BSMC contraction through activation of β-catenin signaling. As β-catenin is a convergence point for many signal pathways, targeting β-catenin may hold promise for the treatment of bladder overactivity. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e9 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kai Li Chuo City, Yamanashi, Japan More articles by this author Jian Yao Chuo, Yamanashi, Japan More articles by this author Norifumi Sawada Chuo, Yamanashi, Japan More articles by this author Tatsuya Miyamoto Chuo, Yamanashi, Japan More articles by this author Masanori Kitamura Chuo, Yamanashi, Japan More articles by this author Masayuki Takeda Chuo, Yamanashi, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...