Collagen-Derived Dipeptide Pro-Hyp Administration Accelerates Muscle Regenerative Healing Accompanied by Less Scarring After Wounding on the Abdominal Wall in Mice

Abstract

Collagens act as cellular scaffolds in extracellular matrixes, and their breakdown products may also have important biological functions. We hypothesize that collagen dipeptide Pro-Hyp induces favorable healing activities and examined the effects of Pro-Hyp administered via different routes on wound healing using our novel murine model, in which an advanced fibrosis-prone scar lesion was developed in the abdominal muscle wall under the skin. After excising a part of the abdominal wall, a free-drinking experiment was performed using solutions with casein (CS), high molecular weight collagen peptides (HP), and low molecular weight collagen peptides including Pro-Hyp and Hyp-Gly (LP), in addition to water (HO). On day 21 of the study, when compared to the HO and CS groups, muscle regeneration in the LP group was significantly advanced in the granulation tissue, which was associated with a decrease in fibrosis. To clarify the effects of Pro-Hyp, daily intraperitoneal administration of pure Pro-Hyp was performed. Pro-Hyp administration induced many myogenically differentiated cells, including myogenin-positive myoblasts and myoglobin-positive myocytes, to migrate in the granulation tissue, while scar tissue decreased. These results indicated that Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall.

Effects of collagen peptide supplementation on cardiovascular markers: a systematic review and meta-analysis of randomised, placebo-controlled trials

“…These dipeptides seem to have signalling effects and promote C2C12 myoblast differentiation and increase myotube hypertrophy by activating the mTOR signalling pathway (18) . The prolyl-hydroxyproline, as other collagen peptides, contain dipeptides (58,59) , accelerates muscle regeneration by inducing several myogenically differentiated cells, including myogenin-positive myoblasts and myoglobin-positive myocytes (59) . Furthermore, it has been revealed that specific collagen peptides could act as signal messengers in anabolic cellular activities in ligaments, tendons and cartilage (15) .…”