Mouse skin fibroblasts with mesenchymal stem cell marker p75 neurotrophin receptor proliferate in response to prolyl-hydroxyproline

Prolyl-hydroxyproline (Pro-Hyp) levels increase in human blood on ingesting collagen hydrolysate and trigger proliferation of primary cultured fibroblasts attached on collagen. Such proliferative effects have been associated with the beneficial effects of collagen hydrolysate ingestion including enhancement of wound healing. However, some fibroblast cell lines do not respond to Pro-Hyp. In this study, we focused on the mesenchymal stem cell marker p75 neurotrophin receptor (p75NTR), because p75NTR-positive cells are increased at wound healing sites. Most fibroblasts that had migrated from the dissected mouse skin for 1-4 days expressed p75NTR. After prolonged cultivation, however, the ratio of p75NTR-positive fibroblasts dropped. The p75NTR-positive fibroblasts specifically incorporated fluorescein isothiocyanate (FITC)-labeled Pro-Hyp and Pro-Hyp significantly increased the number of p75NTR-positive fibroblasts grown on collagen gel. These results suggest that Pro-Hyp could enhance wound healing by stimulating p75NTR-positive fibroblasts at wound healing sites, while it has little effect on p75NTR-negative resident fibroblasts in normal tissues.