Inhibition of ILK restores epithelial ZO-1 and E-cadherin and inhibits fibronectin and Snail1 expression after TGF-β1 treatment. Inhibition of ILK restores.

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Inhibition of ILK restores epithelial ZO-1 and E-cadherin and inhibits fibronectin and Snail1 expression after TGF-β1 treatment. Inhibition of ILK restores epithelial ZO-1 and E-cadherin and inhibits fibronectin and Snail1 expression after TGF-β1 treatment. (A through C) Inhibition of ILK by QLT-0267 preserved the epithelial morphology of HKC-8 cells after TGF-β1 treatment. (D through F) Indirect immunofluorescence staining shows that QLT-0267 treatment restored ZO-1 expression in HKC-8 cells. (H through J) QLT-0267 treatment suppressed the TGF-β1–induced fibronectin expression and its deposition at the extracellular space. (A, D, and H) control. (B, E, and I) TGF-β1 (2 ng/ml). (C, F, and J) TGF-β1 plus QLT-0267 (5 μM). Bar = 20 μm. (G) Western blot analysis demonstrates that QLT-0267 restored E-cadherin expression after treatment with TGF-β1 in HKC-8 cells. HKC-8 cells were incubated with or without TGF-β1 (1 ng/ml) in the absence or presence of different amounts of QLT-0267 as indicated for 48 h. E-cad, E-cadherin. (K) Inhibition of ILK by QLT-0267 reduced the extracellular assembly of fibronectin after TGF-β1 treatment. Extracellular protein extracts were prepared after various treatments as indicated and subjected to Western blot analyses using fibronectin antibody. Fn, fibronectin. (L) Inhibition of ILK suppressed the EMT-regulatory gene Snail1 expression. Snail1 mRNA levels were assessed by quantitative real-time RT-PCR in HKC-8 cells after various treatments as indicated. Yingjian Li et al. JASN 2009;20:1907-1918 ©2009 by American Society of Nephrology