Peters, Andreas S., Brunner, Georg, Blumbach, Katrin, Abraham, David J., Krieg, Thomas and Eckes, Beate (2012). Cyclic mechanical stress downregulates endothelin-1 and its responsive genes independently of TGF beta 1 in dermal fibroblasts. Exp. Dermatol., 21 (10). S. 765 - 771. HOBOKEN: WILEY. ISSN 1600-0625

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Abstract

Mechanical forces are highly variable ranging from the ubiquitous gravity force to compression, fluid shear, torsion, tension and other forms. Mechanical forces act on cells and modulate their biological responses by regulating gene transcription, enzyme and growth factor activity. In soft connective tissues, formation of myofibroblasts strictly requires a mechanically loaded environment in addition to local transforming growth factor (TGF)-beta activity, which itself can be modulated by the mechanical status of the environment. The aim of this study was to monitor the adaptive responses of primary dermal fibroblasts towards cyclic mechanical stress under conditions of high force to better understand the regulation of gene expression in normal skin and mechanisms of gene regulation in mechanically altered fibrotic skin. Primary murine dermal fibroblasts were exposed to equi-biaxial tensile strain. Cyclic mechanical tension was applied at a frequency of 0.1 Hz (69 /min) for 24 h with a maximal increase in surface area of 15%. This treatment resulted in downregulation of alpha smooth muscle actin (alpha SMA) and connective tissue growth factor (CTGF) but not of TGF beta 1 expression. Cyclic strain also strongly reduced endothelin-1 (ET-1) expression and supplementing strained cultures with exogenous ET-1 rescued alpha SMA and CTGF levels. Of note, no biologically significant levels of TGF beta 1 activity were detected in strained cultures. We provide evidence for a novel, TGF beta 1-independent mechanism regulating ET-1 expression in dermal fibroblasts by biomechanical forces. Modulation of ET-1-dependent activities regulates downstream fibrotic marker genes; this pathway might therefore provide an approach to attenuate myofibroblast differentiation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Peters, Andreas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunner, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blumbach, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abraham, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krieg, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckes, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-482381
DOI: 10.1111/exd.12010
Journal or Publication Title: Exp. Dermatol.
Volume: 21
Number: 10
Page Range: S. 765 - 771
Date: 2012
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1600-0625
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TISSUE GROWTH-FACTOR; EXTRACELLULAR-MATRIX; MYOFIBROBLAST DIFFERENTIATION; SYSTEMIC-SCLEROSIS; GRANULATION-TISSUE; TENSILE STRAIN; MESSENGER-RNA; FACTOR-BETA; TENASCIN-C; EXPRESSIONMultiple languages
DermatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48238

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