Collagen-derived dipeptide, proline-hydroxyproline, stimulates cell proliferation and hyaluronic acid synthesis in cultured human dermal fibroblasts

Orally ingested collagen undergoes degradation to small di‐ or tripeptides, which are detected in circulating blood 2 h after ingestion. The influence of collagen‐derived peptides on dermal extracellular matrix components and cell proliferation was studied using cultured human dermal fibroblasts. Of...

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Bibliographic Details
Published in:Journal of dermatology 2010-04, Vol.37 (4), p.330-338
Main Authors: OHARA, Hiroki, ICHIKAWA, Satomi, MATSUMOTO, Hitoshi, AKIYAMA, Minoru, FUJIMOTO, Norihiro, KOBAYASHI, Takashi, TAJIMA, Shingo
Format: Article
Language:English
Subjects:
Cell Proliferation - drug effects
Cells, Cultured
Collagen - metabolism
collagen peptide
Dermis - cytology
Dermis - drug effects
Dermis - metabolism
Dipeptides - metabolism
Dipeptides - pharmacology
Extracellular Matrix - drug effects
Extracellular Matrix - metabolism
fibroblast
Fibroblasts - drug effects
Fibroblasts - metabolism
Genistein - pharmacology
Glucuronosyltransferase - antagonists & inhibitors
Glucuronosyltransferase - genetics
Humans
hyaluronan
Hyaluronan Synthases
hyaluronan synthases 2
Hyaluronic Acid - biosynthesis
Protein Kinase Inhibitors - pharmacology
signal transducer and activator of transcription
STAT3 Transcription Factor - metabolism
Transcription, Genetic - physiology
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Summary:Orally ingested collagen undergoes degradation to small di‐ or tripeptides, which are detected in circulating blood 2 h after ingestion. The influence of collagen‐derived peptides on dermal extracellular matrix components and cell proliferation was studied using cultured human dermal fibroblasts. Of the various collagenous peptides tested here, the dipeptide proline‐hydroxyproline (Pro‐Hyp) enhanced cell proliferation (1.5‐fold) and hyaluronic acid synthesis (3.8‐fold) at a dose of 200 nmol/mL. This was concomitant with a 2.3‐fold elevation of hyaluronan synthase 2 (HAS2) mRNA levels. Small interfering RNA (siRNA)‐mediated knockdown of the HAS2 gene in human dermal fibroblasts inhibited Pro‐Hyp‐induced HAS2 mRNA transcription and cell mitotic activity. Addition of genistein or H7, a protein kinase inhibitor, abolished the Pro‐Hyp‐induced HAS2 mRNA stimulation. Pro‐Hyp elevated phosphorylation of signal transducer and activator of transcription 3 (STAT3) within a short time period (60 min). These results suggest that Pro‐Hyp stimulates both cell mitotic activity and hyaluronic acid synthesis, which is mediated by activation of HAS2 transcription.
ISSN:0385-2407
1346-8138
DOI:10.1111/j.1346-8138.2010.00827.x