Fibroblasts in Mechanically Stressed Collagen Lattices Assume a “Synthetic” Phenotype

TLDR

Fibroblasts experience altered mechanical forces during processes such as wound healing and scar formation, yet the resulting gene expression changes remain poorly understood. Human dermal fibroblasts were cultured in 3‑D collagen lattices under high or low tension, and cDNA microarray combined with Northern blotting identified mechano‑responsive genes involved in extracellular matrix production, growth factor signaling, protease inhibition, focal adhesion, and cytoskeletal organization. Biaxial strain on fibroblasts in silicone membranes produced distinct gene‑regulation patterns, and the collagen‑lattice transcriptional profile indicates that mechanical stimulation induces a synthetic phenotype with enhanced connective‑tissue synthesis and suppressed matrix degradation.

Abstract

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 <i>in vitro</i> 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.