Inhibition of Integrin-Linked Kinase Attenuates Renal Interstitial Fibrosis

• DOI: 10.1681/asn.2008090930
• Publication Date: 2009-06-19T01:10:49Z
• Authors: Yingjian Li; Xiaoyue Tan; Chunsun Dai; Donna B. Stolz; Dan Wang; Youhua Liu
• Keywords: Integrin-linked kinase; GSK3B

Integrin-linked kinase (ILK) is an intracellular serine/threonine protein that regulates cell adhesion, survival, and epithelial-to-mesenchymal transition (EMT). In this study, we investigated the activity of ILK during tubular EMT induced by TGF-beta1 examined therapeutic potential inhibitor in obstructive nephropathy. a biphasic activation renal epithelial cells, with rapid starting at 5 min second wave peaking 24 h; latter paralleled induction expression. Pharmacologic inhibition small-molecule QLT-0267 abolished TGF-beta1-induced phosphorylation Akt glycogen synthase kinase-3beta, suppressed cyclin D1 expression, largely restored expression E-cadherin zonula occludens 1. Inhibition also blocked TGF-beta1-mediated fibronectin, Snail1, plasminogen activator 1, matrix metalloproteinase 2. mouse model nephropathy, administration inhibited beta-catenin accumulation; alpha-smooth muscle actin, vimentin, type I III collagen expression; reduced total tissue content. did not affect kidney structure or function normal mice. These findings suggest increased mediates progression fibrosis. signaling may hold for fibrotic diseases.