Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts – role of TGFß1 levels and RhoA activity

B3 ECKES KRIEG Blumbach K, Zweers MC, Brunner G, Peters AS, Schmitz M, Schulz JN, Schild A, Denton CP, Sakai T, Faessler R, Krieg T, Eckes B. J Cell Sci 123, 872-3883, 2010  

Abstract

Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFβ1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin β1 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 TGFβ1, α-smooth muscle actin (αSMA) production and myofibroblast conversion, which are rescued by exogenous TGFβ1. 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 TGFβ1 levels. We conclude that, in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGFβ1 production, which is essential for dermal repair following injury.

PubMed

 

  • News

  • Upcoming Events

    There are no upcoming events at this time.

  • December 2020
    M T W T F S S
     123456
    78910111213
    14151617181920
    21222324252627
    28293031  

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.

Schließen