Generation of bioactive prolyl‐hydroxyproline (Pro‐Hyp) by oral administration of collagen hydrolysate and degradation of endogenous collagen

Satô, Kenji; Jimi, Shiro; Kusubata, Masashi

doi:10.1111/ijfs.14145

Cited by 19 publications

(13 citation statements)

References 23 publications

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“…Therefore, we concluded that grafted cells could not directly participate in granulation tissue formation, but some components in the tissue suspension solution stimulate the development of granulation tissue. The extracellular components in the solution may contain cytokines [ 26 ], growth factors [ 6 , 27 , 28 ], proteinases [ 29 ] and matrix components [ 30 ], which include tumor necrotic factor, interleukins-1 and 6, transforming growth factor (TGF)-β, vascular endothelial growth factor, FGF, platelet-derived growth factor, epidermal growth factor, hepatocyte growth factor and matrix metalloproteinases, as well as collagens and collagen-derived proline-hydroxyproline peptides [ 31 , 32 ]. All of these factors are candidates of paracrine factors for wound-healing.…”

Section: Discussionmentioning

confidence: 99%

Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension

et al. 2020

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Background and objectives: Skin grafting is a method usually used in reconstructive surgery to accelerate skin regeneration. This method results frequently in unexpected scar formations. We previously showed that cutaneous wound-healing in normal mice is accelerated by a micrograft (MG) technique. Presently, clinical trials have been performed utilizing this technology; however, the driving mechanisms behind the beneficial effects of this approach remain unclear. In the present study, we focused on five major tissue reactions in wound-healing, namely, regeneration, migration, granulation, neovascularization and contraction. Methods: Morphometrical analysis was performed using tissue samples from the dorsal wounds of mice. Granulation tissue formation, neovascularization and epithelial healing were examined. Results: The wound area correlated well with granulation sizes and neovascularization densities in the granulation tissue. Vascular distribution analysis in the granulation tissue indicated that neovessels extended and reached the subepidermal area in the MG group but was only halfway developed in the control group. Moreover, epithelialization with regeneration and migration was augmented by MG. Myofibroblast is a known machinery for wound contraction that uses α-smooth muscle actin filaments. Their distribution in the granulation tissue was primarily found beneath the regenerated epithelium and was significantly progressed in the MG group. Conclusions: These findings indicated that MG accelerated a series of wound-healing reactions and could be useful for treating intractable wounds in clinical situations.

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Section: Discussionmentioning

confidence: 99%

Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension

et al. 2020

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“…The absolute bioavailability of collagen hydrolysates to the small intestine and extra-intestinal tissues in various amino acid and peptide forms is about 90-95% in humans and animals, depending on species and age. In humans, ingestion of collagen hydrolysates increases the concentrations of at least 11 Hyp-containing peptides (Pro-Hyp, Hyp-Gly, Ala-Hyp, Ile-Hyp, Leu-Hyp, Phe-Hyp, Glu-Hyp, Pro-Hyp-Gly, Gly-Pro-Hyp, Ala-Hyp-Gly, and Ser-Hyp-Gly) in plasma (Sato et al 2019). A majority of studies have shown that Pro-Hyp and Hyp-Gly, which are resistant to peptidases in the human plasma, are the most (about 50%) and second most abundant food-derived 4-hydroxyproline-containing peptides in the plasma of healthy adult humans, rats and mice after consuming collagen hydrolysates (Osawa et al 2018;Sato et al 2019;Shigemura et al 2014).…”

Section: Absorption Of 4-hydroxyproline By the Small Intestine And Trmentioning

confidence: 99%

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

2020

Amino Acids

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Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-l-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-l-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and antiinflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.

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“…Pro-Hyp, Leu-Hyp, and Gly-Pro-Hyp were significantly increased in the mouse ear with dermatitis, whereas these peptides did not increase in other ear without dermatitis in the same animal (Kusubata et al, 2015 ; Sato et al, 2019 ). Among these, Pro-Hyp was the most abundant; however, isotope-labeled Pro-Hyp was specifically cleaved in the ear with dermatitis.…”

Section: Generation Of Collagen-derived Di-peptides In Tissuesmentioning

confidence: 97%

Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing

Satô

Asai

Jimi

2020

Front. Cell Dev. Biol.

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Many cells and soluble factors are involved in the wound healing process, which can be divided into inflammatory, proliferative, and remodeling phases. Fibroblasts play a crucial role in wound healing, especially during the proliferative phase, and show heterogeneity depending on lineage, tissue distribution, and extent of differentiation. Fibroblasts from tissue stem cells rather than from healthy tissues infiltrate wounds and proliferate. Some fibroblasts in the wound healing site express the mesenchymal stem cell marker, p75NTR. In the cell culture system, fibroblasts attached to collagen fibrils stop growing, even in the presence of protein growth factors, thus mimicking the quiescent nature of fibroblasts in healthy tissues. Fibroblasts in wound healing sites proliferate and are surrounded by collagen fibrils. These facts indicate presence of new growth-initiating factor for fibroblasts attached to collagen fibrils at the wound healing site, where the collagen-derived peptide, prolyl-hydroxyproline (Pro-Hyp), is generated. Pro-Hyp triggers the growth of p75NTR-positive fibroblasts cultured on collagen gel but not p75NTR-negative fibroblasts. Thus, Pro-Hyp is a low molecular weight growth-initiating factor for specific fibroblasts that is involved in the wound healing process. Pro-Hyp is also supplied to tissues by oral administration of gelatin or collagen hydrolysate. Thus, supplementation of gelatin or collagen hydrolysate has therapeutic potential for chronic wounds. Animal studies and human clinical trials have demonstrated that the ingestion of gelatin or collagen hydrolysate enhances the healing of pressure ulcers in animals and humans and improves delayed wound healing in diabetic animals. Therefore, the low molecular weight fibroblast growth-initiating factor, Pro-Hyp, plays a significant role in wound healing and has therapeutic potential for chronic wounds.

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Generation of bioactive prolyl‐hydroxyproline (Pro‐Hyp) by oral administration of collagen hydrolysate and degradation of endogenous collagen

Cited by 19 publications

References 23 publications

Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension

Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing

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