The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active β1-integrin in adult tendon cells

Ide, Kentaro; Takahashi, Sanai; Sakai, Keiko; Taga, Yuki; Ueno, Takashi; Dickens, David; Jenkins, Rosalind E.; Falciani, Francesco; Sasaki, Takako; Ooi, Kazuhiro; Kawashiri, Shin‐ya; Mizuno, Kazunori; Sakai, Takao

doi:10.1016/j.jbc.2021.100819

“…Yazaki et al indicated that collagen-derived oligopeptides, such as Pro-4Hyp and Gly-Pro-4Hyp, were incorporated into the mouse skin after oral administration of collagen hydrolysate 5 . In addition, several studies reported cellular uptake of collagen-derived oligopeptides, such as by skin fibroblasts 40 , osteoblasts 10 , and tenocytes 12 . Tenocytes are suggested to internalize Pro-4Hyp through multiple pathways, including integrin-mediated endocytosis 12 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

Taga

¹

,

Iwasaki

²

,

Tometsuka

³

et al. 2022

Self Cite

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There are increasing reports demonstrating high bioavailability of 4-hydroxyproline (4Hyp)-containing oligopeptides after oral ingestion of collagen hydrolysate and their bioactivity. In contrast, no study investigates the fate of another collagen-specific but minor amino acid, 3Hyp. Here, we identified Gly-3Hyp-4Hyp tripeptide in human blood at high concentrations, comparable to other 4Hyp-containing oligopeptides, after ingesting porcine skin collagen hydrolysate. Additionally, Gly-3Hyp-4Hyp uniquely maintained the maximum concentration until 4 h after the ingestion due to its exceptionally high resistance to peptidase/protease demonstrated by incubation with mouse plasma. In mice, oral administration of collagen hydrolysate prepared from bovine tendon, which contains a higher amount of 3Hyp, further increased blood Gly-3Hyp-4Hyp levels compared to that from bovine skin. Furthermore, Gly-3Hyp-4Hyp showed chemotactic activity on skin fibroblasts and promoted osteoblast differentiation. These results highlight the specific nature of the Gly-3Hyp-4Hyp tripeptide and its potential for health promotion and disease treatment.

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“…Runx2 and Smad form a transcriptional complex. In a recent study (2021) 20 , it was shown that Pro-Hyp promotes differentiation of tendon cells with modulation of lineage-specific factors and induces chemotactic activity, proliferation, and type I collagen-network organization. In our recent study using primary fibroblasts derived from mouse skin tissue 32 , Pro-Hyp selectively stimulates migration and proliferation of fibroblasts, which express p75 neurotrophin receptor (p75 NTR ) when cultured on collagen gels.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that collagen-derived peptides have biological activities 16 , and ingested hydrolysates accelerate wound healing reactions in patients with pressure ulcers 17 and also enhance anti-aging improvements on the facial skin, including moisture, elasticity, wrinkles, and roughness 18 . Moreover, it has been shown that Pro-Hyp promotes cellular differentiation in osteoblastic cells 19 and tendon cells 20 by modulating intracellular signal pathways.…”

Section: Introductionmentioning

confidence: 99%

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

Jimi

¹

,

Koizumi²,

Satô

³

et al. 2021

Sci Rep

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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.

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“…Runx2 and Smad form a transcriptional complex. In a recent study (2021) 20 , it was shown that Pro-Hyp promotes differentiation of tendon cells with modulation of lineage-speci c factors and induces chemotactic activity, proliferation, and type collagennetwork organization. In our recent study using primary broblasts derived from mouse skin tissue 33 , Pro-Hyp selectively stimulates migration and proliferation of broblasts, which express p75 neurotrophin receptor (p75 NTR ) when cultured on collagen gels.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that collagenderived peptides have biological activities 16 , and ingested hydrolysates accelerate wound healing reactions in patients with pressure ulcers 17 and also enhance anti-aging improvements on the facial skin, including moisture, elasticity, wrinkles, and roughness 18 . Moreover, it has been shown that Pro-Hyp promotes cellular differentiation in osteoblastic cells 19 and tendon cells 20 by modulating intracellular signal pathways.…”

Section: Introductionmentioning

confidence: 99%

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

Jimi

¹

,

Koizumi²,

Sato

³

et al. 2021

Preprint

View full text Add to dashboard Cite

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.

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The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active β1-integrin in adult tendon cells

Abstract: The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodiadriven motility via active β1-integrin in adult tendon cells

Cited by 17 publications

References 93 publications

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

Identification of a highly stable bioactive 3-hydroxyproline-containing tripeptide in human blood after collagen hydrolysate ingestion

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

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

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