Urotensin II promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat.

Abstract

BACKGROUND:

Urotensin II (UII), a potent vasoconstrictive peptide, is able to stimulate phenotypic differentiation of adventitial fibroblasts. This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 (MCP-1) expression in rat aortic adventitial fibroblasts, so as to explore possible mechanisms in the development of vascular inflammation.

METHODS:

Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII (10(-10)-10(-7) mol/L) and inhibitors of signal transduction pathways for 1 to 24 hours. MCP-1 mRNA and protein expression and secretion were determined by RT-PCR, Western blotting analysis and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTS:

UII dose- and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells, with maximal effect at 10(-8) mol/L at 3 hours for mRNA expression, 24 hours for protein expression in the cells, and 12 hours for protein secretion from the cells. Furthermore, the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411, Rho kinase inhibitor Y27632, protein kinase C (PKC) inhibitor H7, mitogen-activated protein kinase inhibitor PD98059, calcineurin inhibitor cyclosporine A, and the Ca(2+)channel blocker nicardipine.

CONCLUSION:

UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase, PKC, mitogen-activated protein kinase, calcineurin and Ca(2+) channel signal transduction, thus contributing to adventitial inflammation.

• Authors: Yonggang Zhang, Shilin Bao, Zejian Kuang, Yanjun Ma, Yanchao Hu, Yanyan Mao
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 127 Issue 10 Pg. 1907-12 ( 2014) ISSN: 2542-5641 [Electronic] China
• PMID: 24824254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL2
• RNA, Messenger
• Urotensins
• urotensin II

Topics

• Adventitia (cytology)
• Animals
• Aorta (cytology)
• Cells, Cultured
• Chemokine CCL2 (genetics, metabolism)
• Fibroblasts (drug effects, metabolism)
• Male
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Urotensins (pharmacology)