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β-Catenin Signaling Contributes to Platelet Derived Growth Factor Elicited Bladder Smooth Muscle Cell Contraction Through Up-Regulation of Cx43 Expression

2012; Lippincott Williams & Wilkins; Volume: 188; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2012.02.2556

1527-3792

Kai Li, Jian Yao, Norifumi Sawada, Masanori Kitamura, Karl‐Erik Andersson, Masayuki Takeda,

Urological Disorders and Treatments

No AccessJournal of UrologyInvestigative Urology1 Jul 2012β-Catenin Signaling Contributes to Platelet Derived Growth Factor Elicited Bladder Smooth Muscle Cell Contraction Through Up-Regulation of Cx43 Expression Kai Li, Jian Yao, Norifumi Sawada, Masanori Kitamura, Karl-Erik Andersson, and Masayuki Takeda Kai LiKai Li Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan Department of Oncology, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China More articles by this author , Jian YaoJian Yao Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author , Norifumi SawadaNorifumi Sawada Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan Wake Forest Regenerative Medicine, Winston-Salem, North Carolina More articles by this author , Masanori KitamuraMasanori Kitamura Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author , Karl-Erik AnderssonKarl-Erik Andersson Wake Forest Regenerative Medicine, Winston-Salem, North Carolina More articles by this author , and Masayuki TakedaMasayuki Takeda Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2556AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Increased gap junctions contribute to bladder overactivity but the factors and mechanisms involved in gap junction regulation in the bladder are not well established. We examined whether and how platelet derived growth factor regulates connexin43 in bladder smooth muscle cells. Materials and Methods: Cultured rat bladder smooth muscle cells were treated with growth factors with or without agents that interfere with phosphatidylinositol 3-kinase, mitogen activated protein kinase and β-catenin signaling pathways. Connexin43 expression was examined by Western and Northern blot, and immunochemistry. Functional gap junctions were evaluated by scrape-loading dye transfer assay. Bladder smooth muscle cell contraction was measured by collagen gel contraction. Results: 1) Platelet derived growth factor induced phosphatidylinositol 3-kinase and mitogen activated protein kinase dependent accumulation of nuclear β-catenin. This was followed by increased connexin43 expression. 2) Down-regulation of β-catenin by specific siRNA abolished the connexin43 increasing effect of platelet derived growth factor while β-catenin stimulation due to glycogen synthase kinase inhibition mimicked that effect. 3) Basic fibroblast growth factor and epidermal growth factor also induced connexin43 expression. Their effects were potentiated by platelet derived growth factor. 4) Gap junction inhibition attenuated the bladder smooth muscle cell contraction induced by platelet derived growth factor. Consistently fibroblasts from connexin43 knockout (Cx43−/−) mice showed a much weaker contractile response to platelet derived growth factor than cells from connexin43-wild (Cx43+/+) litter mates. Conclusions: Platelet derived growth factor induces connexin43 expression and bladder smooth muscle cell contraction by activating β-catenin signaling. 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Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 188Issue 1July 2012Page: 307-315 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordsmuscle contractionurinary bladdermusclesmoothbeta cateninplatelet-derived growth factoroveractiveMetricsAuthor Information Kai Li Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan Department of Oncology, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China More articles by this author Jian Yao Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author Norifumi Sawada Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan Wake Forest Regenerative Medicine, Winston-Salem, North Carolina More articles by this author Masanori Kitamura Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author Karl-Erik Andersson Wake Forest Regenerative Medicine, Winston-Salem, North Carolina More articles by this author Masayuki Takeda Department of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan More articles by this author Expand All Advertisement PDF downloadLoading ...