Universität zu Köln

Blumbach, Katrin, Zweers, Manon C., Brunner, Georg, Peters, Andreas S., Schmitz, Markus, Schulz, Jan-Niklas ORCID: 0000-0001-9286-206X, Schild, Alexander, Denton, Christopher P., Sakai, Takao, Faessler, Reinhard, Krieg, Thomas and Eckes, Beate (2010). Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts - role of TGF beta 1 levels and RhoA activity. J. Cell Sci., 123 (22). S. 3872 - 3884. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 0021-9533

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Abstract

Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGF beta 1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin beta 1 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 TGF beta 1, alpha-smooth muscle actin (alpha SMA) production and myofibroblast conversion, which are rescued by exogenous TGF beta 1. 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 TGF beta 1 levels. We conclude that, in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGF beta 1 production, which is essential for dermal repair following injury.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Blumbach, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zweers, Manon C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunner, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Andreas S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Jan-Niklas UNSPECIFIED orcid.org/0000-0001-9286-206X UNSPECIFIED Schild, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Denton, Christopher P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sakai, Takao UNSPECIFIED UNSPECIFIED UNSPECIFIED Faessler, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-492495
DOI:	10.1242/jcs.063024
Journal or Publication Title:	J. Cell Sci.
Volume:	123
Number:	22
Page Range:	S. 3872 - 3884
Date:	2010
Publisher:	COMPANY OF BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	0021-9533
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR-BETA; HAIR FOLLICLE MORPHOGENESIS; ACTIVATES LATENT TGF-BETA-1; CELL-ADHESION; EXTRACELLULAR-MATRIX; TGF-BETA; MYOFIBROBLAST DIFFERENTIATION; FOCAL ADHESIONS; SMOOTH-MUSCLE; WOUND REPAIR Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49249