Attachment-regulated signaling networks in the fibroblast-populated 3D collagen matrix

Fibroblasts in the attached collagen matrix are in a pro-survival, pro-proliferative state relative to fibroblasts in the released collagen matrix, such that matrix cell number increases in the former over time. Gene array data from attached vs. released matrices were analyzed for putative networks that regulated matrix cell number. Select networks then underwent augmentation and/or inhibition in order to determine their biologic relevance. Matrix stress-release was associated with modulation of signaling networks that involved IL6, IL8, NF-κB, TGF-β1, p53, interferon-γ, and other entities as central participants. Perturbation of select networks in multiple fibroblast strains suggested that IL6 and IL8 secretion may have been involved in preservation of matrix cell population in the released matrix, though there was variability in testing results among the strains. NF-κB activation may have contributed to the induction of population regression after matrix release.