Salmon nasal cartilage proteoglycan enhances growth of normal human dermal fibroblast through Erk1/2 phosphorylation

Biosci Biotechnol Biochem. 2017 Jul;81(7):1379-1385. doi: 10.1080/09168451.2017.1318695. Epub 2017 May 2.

Abstract

Proteoglycan (PG) is a heavily glycosylated protein, localized to cell surface and extracellular matrix, and has various functions. Recently, it has been gradually revealed that PG interacts with various growth factors and morphogens and regulates cellular functions. Although salmon nasal cartilage PG (Salmon-PG) increases proliferation of immortalized cells, its mechanism remains unclear. In this study, we confirmed the effect of Salmon-PG on normal human dermal fibroblast (NHDF) and investigated the mechanism of PG action on NHDF. Salmon-PG dose- and time-dependently increased NHDF proliferation. Receptor tyrosine kinase array revealed that Salmon-PG increased only Erk1/2 signaling. Erk1/2 phosphorylation was significantly increased by Salmon-PG in a time-(10 min) and dose-(400 or 800 μg/mL) dependent manner. MEK inhibitor suppressed the enhancement of NHDF proliferation by Salmon-PG. The overall findings indicate that Salmon-PG plays a role as a growth factor in NHDF via Erk1/2 activation, suggesting that Salmon-PG contributes to the maintenance of skin homeostasis.

Keywords: Erk phosphorylation; cell growth; normal human dermal fibroblast; proteoglycan.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dermis / cytology
  • Dermis / drug effects*
  • Dermis / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Flavonoids / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Microarray Analysis
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nasal Cartilages / chemistry*
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Proteoglycans / isolation & purification
  • Proteoglycans / pharmacology*
  • Salmon
  • Signal Transduction

Substances

  • Flavonoids
  • Protein Kinase Inhibitors
  • Proteoglycans
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one