Role of Dlg5/lp-dlg, a Membrane-Associated Guanylate Kinase Family Protein, in Epithelial-Mesenchymal Transition in LLc-PK1 Renal Epithelial Cells

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From: PLoS ONE(Vol. 7, Issue 4)
Publisher: Public Library of Science
Document Type: Article
Length: 7,308 words
Lexile Measure: 1310L

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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-[beta] (TGF-[beta])-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 [alpha]-smooth muscle actin, and suppressed the expression of E-cadherin. In addition, activation of JNK and p38, which are stimulated by TGF-[beta], was enhanced by Dlg5 depletion. Furthermore, inhibition of the TGF-[beta] receptor suppressed the effects of Dlg5 depletion. These observations suggest that Dlg5 is involved in the regulation of TGF-[beta]receptor-dependent signals and EMT.

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Gale Document Number: GALE|A477051665