| First Author | Blumbach K | Year | 2010 |
| Journal | J Cell Sci | Volume | 123 |
| Issue | Pt 22 | Pages | 3872-83 |
| PubMed ID | 20980390 | Mgi Jnum | J:182911 |
| Mgi Id | MGI:5317073 | Doi | 10.1242/jcs.063024 |
| Citation | Blumbach K, et al. (2010) Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts - role of TGFbeta1 levels and RhoA activity. J Cell Sci 123(Pt 22):3872-83 |
| abstractText | Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFbeta1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin beta1 tails in focal adhesions mediating the communication between cells and extracellular matrix. Here, we show that fibroblast-restricted inactivation of ILK in mice leads to impaired healing due to a severe reduction in the number of myofibroblasts, whereas inflammatory infiltrate and vascularization of the granulation tissue are unaffected. Primary ILK-deficient fibroblasts exhibit severely reduced levels of extracellular TGFbeta1, alpha-smooth muscle actin (alphaSMA) production and myofibroblast conversion, which are rescued by exogenous TGFbeta1. They are further characterized by elevated RhoA and low Rac1 activities, resulting in abnormal shape and reduced directional migration. Interference with RhoA-ROCK signaling largely restores morphology, migration and TGFbeta1 levels. We conclude that, in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGFbeta1 production, which is essential for dermal repair following injury. |
