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

Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

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-phosphospecific 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.

Original languageEnglish
Pages (from-to)3385-3391
Number of pages7
JournalWorld Journal of Gastroenterology
Volume11
Issue number22
DOIs
Publication statusPublished - 2005 Jun 14

Keywords

  • Janus kinase
  • Pancreatic fibrosis
  • Pancreatic stellate cells
  • Pancreatitis
  • Platelet-derived growth factor
  • Signal transducers and activators of transcription

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells'. Together they form a unique fingerprint.

Cite this