Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2005; 11(22): 3385-3391
Published online Jun 14, 2005. doi: 10.3748/wjg.v11.i22.3385
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
Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Author contributions: All authors contributed equally to the work.
Supported by the grant-in-aid of Encouragement of Young Scientists from Japan Society for the Promotion of Science, No. 16590572, Pancreas Research Foundation of Japan No. 01-01, and the Kanae Foundation for Life and Socio-Medical Science
Correspondence to: Dr. Atsushi Masamune, Division of Gastroe-nterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cyo, Aoba-ku, Sendai 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp
Telephone: +81-22-717-7171 Fax: +81-22-717-7177
Received: August 26, 2004
Revised: August 27, 2004
Accepted: August 27, 2004
Published online: June 14, 2005
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.

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