TENASCIN-C EXPRESSION BY FIBROBLASTS IS ELEVATED IN STRESSED COLLAGENGELS

Chick embryo fibroblasts cultured on a collagen matrix exert tractiona l forces leading to the contraction of unrestrained, floating collagen gels and to the development of tension in attached, restrained gels. On a restrained, attached collagen gel the fibroblasts synthesize larg e quantities of tenascin-C, whereas in a floating, contracting gel ten ascin-C synthesis is decreased. This regulation of tenascin-C synthesi s can be observed by the secretion of metabolically labeled tenascin-C into the conditioned medium, as well as by the deposition of tenascin -C into the collagen matrix as judged by immunofluorescence. Regulatio n appears to occur at the transcriptional level, because when cells on attached or floating collagen gels are transfected with promoter cons tructs of the tenascin-C gene, luciferase expression driven by the ten ascin-C promoter parallels the effects measured for endogenous tenasci n-C synthesis, whereas luciferase expression under the control of the SV40 promoter does not depend on the state of the collagen gel. The pr omoter region responsible for tenascin-C induction on attached collage n gels is distinct from the region important for the induction of tena scin-C by serum, and may define a novel kind of response element. By j oining this tenascin-C sequence to the SV40 promoter of a reporter pla smid, its activity can be transferred to the heterologous promoter. We propose that the tenascin-C promoter is directly or indirectly activa ted in fibroblasts generating and experiencing mechanical stress withi n a restrained collagen matrix. This may be an important aspect of the regulation of tenascin-C expression during embryogenesis as well as d uring wound healing and other regenerative and morphogenetic processes .