Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells

World J Gastroenterol. 2005 Jun 14;11(22):3385-91. doi: 10.3748/wjg.v11.i22.3385.


Aim: To clarify the role of Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs).

Methods: PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2, STAT1, STAT3, and ERK was determined by Western blotting using anti-phospho-specific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine.

Results: PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGF-induced activation of STAT1 and STAT3 was inhibited by a Src inhibitor PP1 and a JAK2 inhibitor AG490, whereas PDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense oligonucleotide.

Conclusion: PDGF-BB activated JAK2-STAT pathway via Src-dependent mechanism. Activation of JAK2-STAT3 pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Cell Division / drug effects
  • Cell Division / physiology
  • DNA-Binding Proteins / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Janus Kinase 2
  • Male
  • Pancreas / cytology*
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Rats, Wistar
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Trans-Activators / metabolism*
  • src-Family Kinases / metabolism


  • DNA-Binding Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-sis
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, rat
  • Stat3 protein, rat
  • Trans-Activators
  • Becaplermin
  • Protein-Tyrosine Kinases
  • Jak2 protein, rat
  • Janus Kinase 2
  • src-Family Kinases
  • Extracellular Signal-Regulated MAP Kinases