RGD Reference Report - Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells. - Rat Genome Database

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Role of JAK/STAT pathway in IL-6-induced activation of vascular smooth muscle cells.

Authors: Watanabe, S  Mu, W  Kahn, A  Jing, N  Li, JH  Lan, HY  Nakagawa, T  Ohashi, R  Johnson, RJ 
Citation: Watanabe S, etal., Am J Nephrol. 2004 Jul-Aug;24(4):387-92. Epub 2004 Jul 9.
RGD ID: 1641933
Pubmed: PMID:15256805   (View Abstract at PubMed)
DOI: DOI:10.1159/000079706   (Journal Full-text)

BACKGROUND/AIMS: IL-6, an inducer of the acute-phase response, is linked with the development of vascular disease and atherosclerosis. One mechanism likely involves direct effects of IL-6 on vascular smooth muscle cells (VSMC), for IL-6 can induce VSMC proliferation and the release of monocyte chemoattractant protein-1 (MCP-1). We hypothesized that this stimulation occurs via the JAK (janus-activated kinase)/STAT (signal and transducers and activators of transcription) signaling pathway. METHODS: Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 (by Western), MCP-1 (by ELISA) and DNA synthesis (by (3)H-thymidine incorporation) was determined. RESULTS: IL-6 rapidly induced phosphorylation of STAT 3 in a dose- and time-dependent manner with a peak expression at 30 min. IL-6 also stimulated MCP-1 protein production and DNA synthesis dose dependently. 50 microM of AG490, a specific JAK 2 inhibitor, partially inhibited STAT 3 activation and MCP-1 production, with near complete inhibition of DNA synthesis. CONCLUSION: The JAK/STAT pathway partially mediates IL-6-induced MCP-1 production and DNA synthesis in rat VSMC. These studies implicate a role of the JAK/STAT pathway in the development of vascular disease and atherosclerosis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell activation  IMP 1641933vascular smooth muscle cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Jak2  (Janus kinase 2)


Additional Information