Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro

The biochemical regulation of collagen deposition during adult cutaneous wo und repair is poorly understood. Likewise, how collagen is perceived and mo dulated in fetal scarless healing remains unknown. Recently, discoidin doma in receptors-1 and 2 (DDR1 and DDR2) with tyrosine kinase activity have bee n identified as novel receptors for collagen. In light of these findings, i t was speculated that the production of collagen receptors DDR1 and DDR2 by fetal fibroblasts may be temporally regulated to correlate with the ontoge ny of embryonic scar formation. More specifically, because DDRs directly bi nd collagen and transmit the signals intracellularly, it was hypothesized t hat they may play an important role in fetal scarless healing by ultimately regulating and modulating collagen production and organization. As part of a fundamental assessment to elucidate the role of DDRs in scarless fetal w ound repair, the endogenous expression of DDR1, DDR2, collagen I, and total collagen, as a function of fetal Sprague-Dawley rat skin fibroblasts of di fferent gestational ages, representing scar-free (<E16.5 days) and scar-for ming (>E16.5) periods was determined. Using explanted dermal fibroblasts of gestational days E13.5, E16.5, E18.5, and E21.5 (term gestation = 21.5 day s) fetuses (n = 92), [H-3] proline incorporation assay and Northern and Wes tern blotting analysis were performed to compare the expressions of these m olecules with scar-free and scar-forming stages of embryonic development. T hese results revealed a pattern of increasing collagen production with incr easing gestational ages,whereas DDR1 expression decreased with increasing g estational age. This observation suggests that elevated levels of DDR1 may play an important role in scarless tissue regeneration by early gestation f etal fibroblasts. In contrast, DDR2 was expressed by fetal rat fibroblasts at a similar level throughout gestation. These data demonstrate for the fir st time the temporal expression of collagen and DDR tyrosine kinases in fet al rat fibroblasts as a function of gestational ages. Overall, these data s uggest that differential temporal expression of the above-mentioned molecul es during fetal skin development may play an important role in the ontogeny of scar formation. Future studies will involve the characterization of the biomolecular functions of these receptor kinases during fetal wound repair .