Title Role of Dlg 5 / lp-dlg , a Membrane-Associated Guanylate Kinase Family Protein , in Epithelial-Mesenchymal Transition in LLc-PK 1 Renal Epithelial Cells

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-b (TGF-b)-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 a-smooth muscle actin, and suppressed the expression of E-cadherin. In addition, activation of JNK and p38, which are stimulated by TGF-b, was enhanced by Dlg5 depletion. Furthermore, inhibition of the TGF-b receptor suppressed the effects of Dlg5 depletion. These observations suggest that Dlg5 is involved in the regulation of TGF-breceptor-dependent signals and EMT. Citation: Sezaki T, Inada K, Sogabe T, Kakuda K, Tomiyama L, et al. (2012) Role of Dlg5/lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells. PLoS ONE 7(4): e35519. doi:10.1371/journal.pone.0035519 Editor: Cara Gottardi, Northwestern University Feinberg School of Medicine, United States of America Received October 24, 2011; Accepted March 17, 2012; Published April 23, 2012 Copyright: 2012 Sezaki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported in part by the Mishima Kaiun Memorial Foundation; the Asahi Glass Foundation; a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; a grant from the Bio-oriented Technology Research Advancement Institution; and Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: nkioka@kais.kyoto-u.ac.jp . These authors contributed equally to this work.