Role of Dlg5/lp-dlg, a membrane-associated guanylate kinase family protein, in epithelial-mesenchymal transition in LLc-PK1 renal epithelial cells

PLoS One. 2012;7(4):e35519. doi: 10.1371/journal.pone.0035519. Epub 2012 Apr 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cadherins / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Fibronectins / metabolism
  • Guanylate Kinases / antagonists & inhibitors
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • LLC-PK1 Cells / drug effects
  • LLC-PK1 Cells / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism
  • Swine
  • Transforming Growth Factor beta / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Actins
  • Cadherins
  • Fibronectins
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Guanylate Kinases