title: Caveolin 3-mediated integrin β1 signaling is required for the proliferation of folliculostellate cells in rat anterior pituitary gland under the influence of extracellular matrix.
abstract: Folliculostellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture exhibited marked proliferation in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. In a process referred to as matricrine action, FS cells receive ECM as a signal through their receptors, which results in morphological and functional changes. In this study, we investigated matricrine signaling in FS cells and observed that the proliferation of FS cells is mediated by integrin β1, which is involved in various signaling pathways for cell migration and proliferation in response to ECM. Then, we analyzed downstream events of the integrin β1 signaling pathway in the proliferation of FS cells and identified caveolin 3 as a potential candidate molecule. Caveolin 3 is a membrane protein that binds cholesterol and a number of signaling molecules that interact with integrin β1. Using specific small interfering RNA of caveolin 3, the proliferation of FS cells was inhibited. Furthermore, caveolin 3 drove activation of the mitogen-activated protein kinase (MAPK) signaling cascades, which resulted in upregulation of cyclin D1 in FS cells. These findings suggest that matricrine signaling in the proliferation of FS cells was transduced by a caveolin 3-mediated integrin β1 signaling pathway and subsequent activation of the MAPK pathway.
authors.affiliation: Division of Histology and Cell Biology, Department of Anatomy, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. kota@jichi.ac.jp
authors.forename: Kotaro
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Cimi
authors.initials: C
authors.lastname: Ilmiawati
authors.forename: Motoshi
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Tsukada
authors.forename: Tom
authors.initials: T
authors.lastname: Kouki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yashiro
mesh_terms: D000818:Animals; D021941:Caveolae / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051244:Caveolin 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D049109:Cell Proliferation; D002478:Cells, Cultured; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000502:physiology*; D020868:Gene Silencing; D017930:Genes, Reporter; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000502:physiology; D020935:MAP Kinase Signaling System; D008297:Male; D018715:Microscopy, Video; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D055647:Rats, Transgenic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C495537:Cav1 protein, rat; C495549:Cav3 protein, rat; D051242:Caveolin 1; D051244:Caveolin 3; D019012:Integrin beta1; D007797:Laminin; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat