Fibroblasts in mechanically stressed collagen lattices assume a "synthetic" phenotype.
Fibroblasts are subjected to changes of the mechanical force balance during physiological as well as pathological situations, such as wound healing, development of hypertrophic scars, and fibrogenesis. However, the molecular response and the changes in fibroblast gene expression upon mechanical stimulation remain poorly understood. As an in vitro model, human dermal fibroblasts were cultured within a three-dimensional network of fibrillar collagen either under high (stressed) or low tension (relaxed). cDNA microarray technology in combination with Northern blot analysis led to identification of mechano-responsive genes coding for extracellular matrix proteins, fibrogenic growth factors, protease inhibitors, components of focal adhesions, and the cytoskeleton. Application of biaxial strain to fibroblasts cultured on flexible silicone membranes revealed that the type of strain as well as the properties of the substrate induced different patterns of gene regulation. The transcriptional profile of mechanically induced genes in collagen lattices suggests that mechanical stimuli lead to a "synthetic" fibroblast phenotype characterized by induction of connective tissue synthesis while simultaneously inhibiting matrix degradation.
Kessler
D
D
Department of Dermatology, Joseph-Stelzmann Strasse 9, University of Cologne, 50931 Köln, Germany.
Dethlefsen
S
S
Haase
I
I
Plomann
M
M
Hirche
F
F
Krieg
T
T
Eckes
B
B
D000199:Actins / Q000096:biosynthesis; D015152:Blotting, Northern; D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D016596:Vinculin / Q000096:biosynthesis; D014945:Wound Healing
D000199:Actins; C526317:CCN2 protein, human; D018076:DNA, Complementary; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D016596:Vinculin; D055513:Connective Tissue Growth Factor; D003094:Collagen