THE ROLE OF INTEGRIN-LINKED KINASE IN TGF-ß1 INDUCTION OF DERMAL MYOFIBROBLAST DIFFERENTIATION

Dermal wound contraction involves the transition of fibroblasts to myofibroblasts. This process requires stimulation of Transforming Growth Factor (TGF)-P receptors activation and signals triggered by development of matrix tension. While TGF-pi signalling is driven predominantly by Smad2/3 signalling, mechanotransduction is achieved mainly through integrin-mediated events. Integrin-linked kinase (ILK) is a multifunctional scaffolding protein that interacts with integrins to transmit signals from the extracellular matrix to the cell. The purpose of this study is to determine the roles of ILK in dermal fibroblasts. Hence, I demonstrate that ILK is required for TGF-pi- induced dermal myofibroblast differentiation and that ILK-deficient dermal fibroblasts display reduced ability to contract collagen matrices. ILK deficiency also attenuated TGF-pi induction of Smad2 phosphorylation, implicating ILK in TGF-pi signalling. I further showed that ILK interacts with TGF-p receptor type II (TPRII), and that it is required for TPRII stability. Ultimately, my study identifies a novel modulatory role for ILK in TGF-p 1 signalling, which regulates dermal fibroblast to myofibroblast transition