Induction of tenascin-C by cyclic tensile strain versus growth factors: distinct contributions by Rho/ROCK and MAPK signaling pathways.
Expression of the extracellular matrix (ECM) protein tenascin-C is induced in fibroblasts by growth factors as well as by tensile strain. Mechanical stress can act on gene regulation directly, or indirectly via the paracrine release of soluble factors by the stimulated cells. To distinguish between these possibilities for tenascin-C, we asked whether cyclic tensile strain and soluble factors, respectively, induced its mRNA via related or separate mechanisms. When cyclic strain was applied to chick embryo fibroblasts cultured on silicone membranes, tenascin-C mRNA and protein levels were increased twofold within 6 h compared to the resting control. Medium conditioned by strained cells did not stimulate tenascin-C mRNA in resting cells. Tenascin-C mRNA in resting cells was increased by serum; however, cyclic strain still caused an additional induction. Likewise, the effect of TGF-beta1 or PDGF-BB was additive to that of cyclic strain, whereas IL-4 or H2O2 (a reactive oxygen species, ROS) did not change tenascin-C mRNA levels. Antagonists for distinct mitogen-activated protein kinases (MAPK) inhibited tenascin-C induction by TGF-beta1 and PDGF-BB, but not by cyclic strain. Conversely, a specific inhibitor of Rho-dependent kinase strongly attenuated the response of tenascin-C mRNA to cyclic strain, but had limited effect on induction by growth factors. The data suggest that regulation of tenascin-C in fibroblasts by cyclic strain occurs independently from soluble mediators and MAPK pathways; however, it requires Rho/ROCK signaling.
Chiquet
Matthias
M
ITI-Research Institute for Dental and Skeletal Biology, University of Bern, Murtenstrasse 35, P.O. Box 54, CH-3010 Bern, Switzerland. matthias.chiquet@iti.unibe.ch
Sarasa-Renedo
Ana
A
Tunç-Civelek
Vildan
V
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013314:Stress, Mechanical; D019063:Tenascin / Q000096:biosynthesis* / Q000235:genetics; D054460:rho-Associated Kinases
D017077:Culture Media, Conditioned; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019063:Tenascin; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases