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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."xsd:string
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http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/author"Shimosegawa T."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/author"Suzuki N."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/author"Satoh M."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/author"Masamune A."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/author"Kikuta K."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/name"World J Gastroenterol"xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/pages"3385-3391"xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/title"Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells."xsd:string
http://purl.uniprot.org/citations/15948243http://purl.uniprot.org/core/volume"11"xsd:string
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