title: Role of Dlg5/lp-dlg, a membrane-associated guanylate kinase family protein, in epithelial-mesenchymal transition in LLc-PK1 renal epithelial cells.
abstract: Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase adaptor family of proteins, some of which are involved in the regulation of epithelial-to-mesenchymal transition (EMT). Dlg5 has been described as a susceptibility gene for Crohn's disease; however, the physiological function of Dlg5 is unknown. We show here that transforming growth factor-β (TGF-β)-induced EMT suppresses Dlg5 expression in LLc-PK1 cells. Depletion of Dlg5 expression by knockdown promoted the expression of the mesenchymal marker proteins, fibronectin and α-smooth muscle actin, and suppressed the expression of E-cadherin. In addition, activation of JNK and p38, which are stimulated by TGF-β, was enhanced by Dlg5 depletion. Furthermore, inhibition of the TGF-β receptor suppressed the effects of Dlg5 depletion. These observations suggest that Dlg5 is involved in the regulation of TGF-βreceptor-dependent signals and EMT.
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
authors.forename: Takuhito
authors.initials: T
authors.lastname: Sezaki
authors.forename: Kohki
authors.initials: K
authors.lastname: Inada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sogabe
authors.forename: Kumiyo
authors.initials: K
authors.lastname: Kakuda
authors.forename: Lucia
authors.initials: L
authors.lastname: Tomiyama
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Michinori
authors.initials: M
authors.lastname: Matsuo
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Ueda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D051528:Guanylate Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018374:LLC-PK1 Cells / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D005353:Fibronectins; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D051528:Guanylate Kinases