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IP-10/CXCR3 Axis Promotes the Proliferation of Vascular Smooth Muscle Cells through ERK1/2/CREB Signaling Pathway.

Abstract：

:Excessive proliferation of vascular smooth muscle cells is one of the main pathological processes leading to atherosclerosis and intimal hyperplasia after vascular interventional therapy. Our previous study has shown that interferon-γ inducible protein-10 contributes to the proliferation of vascular smooth muscle cell. However, the underlying mechanisms remain unclear. Extracellular signal-regulated kinase 1/2, serine/threonine kinase Akt, and cAMP response element binding protein are signaling pathways, which are considered to play important roles in the processes of vascular smooth muscle cell proliferation. Moreover, chemokine receptor 3 and Toll-like receptor 4 are potential receptors of inducible protein-10 in this process. In the present study, IP-10 was found to directly induce vascular smooth muscle cell proliferation, and exposure to inducible protein-10 activated extracellular signal-regulated kinase 1/2, serine/threonine kinase, and cAMP response element binding protein signaling. Inhibitor of extracellular signal-regulated kinase 1/2, rather than inhibitor of serine/threonine kinase, inhibited the phosphorylation of cAMP response element binding protein and reduced inducible protein-10-stimulated vascular smooth muscle cell proliferation. Knockdown of cAMP response element binding protein by siRNA inhibited inducible protein-10-induced vascular smooth muscle cell proliferation. Moreover, anti-CXCR3 IgG, instead of anti-Toll-like receptor 4 IgG, reduced inducible protein-10-induced vascular smooth muscle cell proliferation and inducible protein-10-stimulated extracellular signal-regulated kinase 1/2 and cAMP response element binding protein activation. Together, these results indicate that inducible protein-10 promotes vascular smooth muscle cell proliferation via chemokine receptor 3 and activation of extracellular signal-regulated kinase 1/2 inducible protein-10-induced vascular smooth muscle cell proliferation. These data provide important targets for future studies to modulate atherosclerosis and restenosis after vascular interventional therapy.

journal_name

Cell Biochem Biophys

journal_title

Cell biochemistry and biophysics

authors

Wang HJ,Zhou Y,Liu RM,Qin YS,Cen YH,Hu LY,Wang SM,Hu ZJ

doi

10.1007/s12013-017-0782-9

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

139-147

issue

eissn

1085-9195

issn

1559-0283

pii

10.1007/s12013-017-0782-9

journal_volume

pub_type

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IP-10/CXCR3 Axis Promotes the Proliferation of Vascular Smooth Muscle Cells through ERK1/2/CREB Signaling Pathway.