PD98059 inhibits expression of pERK1 protein and collagen alpha1(I) mRNA in rat pancreatic stellate cells activated by platelet-derived growth factor

Indian J Gastroenterol. 2005 May-Jun;24(3):100-3.

Abstract

Objective: Pancreatic stellate cells (PSC) are considered as the principal effector cells in pancreatic fibrosis. We studied the role of platelet-derived growth factor (PDGF) in the activation of PSC.

Methods: Cultured rat PSC were co-incubated with PDGF-BB (25 ng/mL) and different doses (0-40 ng/mL) of PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK). Expressions of p ERK1 protein and of collagen a1(I) mRNA were measured.

Results: Expression of p ERK1 protein was up-regulated by PDGF-BB, and was down-regulated in a dose-dependent manner by PD98059. Expression of collagen a1(I) mRNA also showed an increase with PDGF-BB and non-dose-dependent inhibition by PD98059.

Conclusion: Our findings suggest that PSC activation is mediated by PDGF signal pathway, and ERK1 protein plays an important role in this activation.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Collagen Type I / antagonists & inhibitors*
  • Flavonoids / pharmacology*
  • Male
  • Pancreas / cytology*
  • Platelet-Derived Growth Factor / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • eIF-2 Kinase / antagonists & inhibitors*

Substances

  • Collagen Type I
  • Flavonoids
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • PERK kinase
  • eIF-2 Kinase
  • Calcium-Calmodulin-Dependent Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one