Collagen-derived dipeptide Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall in mice

Shiro Jimi,Seiko Koizumi,Arman Saparov,Kenji Sato,Motoyasu Miyazaki

doi:10.1038/s41598-021-98407-9

Shiro Jimi, Seiko Koizumi + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-98407-9

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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.

Highlights

IntroductionIn the case of skeletal muscle injury, satellite cells in the muscular fasciae are stimulated to replicate and differentiate into myoblasts, and they fuse and form myotubes, and thereafter they are functionally maturated into regenerated myofiber rich myocytes
Injury generates different responses in different organs
The major types are: type I, which is rich in the dermis, ligament, and tendon, type II, which is found in the cartilage, type IV distributes in the basal membrane, and types I and III are found in the granulation tissue

Summary

Introduction

In the case of skeletal muscle injury, satellite cells in the muscular fasciae are stimulated to replicate and differentiate into myoblasts, and they fuse and form myotubes, and thereafter they are functionally maturated into regenerated myofiber rich myocytes. These sequential morphological alterations in the myogenesis of the skeletal muscle have been intensively investigated[11], but their responses in wound healing are still uncertain. We have established the wound healing model by excising a part of the abdominal wall in mice without any device or chemical, in which scar lesion and muscle regeneration simultaneously occur in the granulation tissue. We focused on the morphological alterations of fibrous scar lesions and muscle differentiation in the granulation tissue in mice treated with Pro-Hyp and found that Pro-Hyp is useful in reducing scarring and increasing muscle regeneration in the granulation tissue on the abdominal muscle wall

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