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Jeong JY, Son Y, Kim BY, et al. Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells. Korean J Physiol Pharmacol. 2015;19(6):549-55doi: 10.4196/kjpp.2015.19.6.549.
Jeong, J. Y., Son, Y., Kim, B. Y., Eo, S. K., Rhim, B. Y., & Kim, K. (2015). Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 19(6), 549-55. https://doi.org/10.4196/kjpp.2015.19.6.549
Jeong, Ji Young, et al. "Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells." The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology vol. 19,6 (2015): 549-55. doi: https://doi.org/10.4196/kjpp.2015.19.6.549
Jeong JY, Son Y, Kim BY, Eo SK, Rhim BY, Kim K. Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells. Korean J Physiol Pharmacol. 2015 Nov;19(6):549-55. doi: 10.4196/kjpp.2015.19.6.549. Epub 2015 Oct 16. PMID: 26557022; PMCID: PMC4637358.
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Korean J Physiol Pharmacol. 2015 Nov;19(6):549-55. doi: 10.4196/kjpp.2015.19.6.549. Epub 2015 Oct 16.

Multiple Signaling Pathways Contribute to the Thrombin-induced Secretory Phenotype in Vascular Smooth Muscle Cells.

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology

Ji Young Jeong, Younghae Son, Bo-Young Kim, Seong-Kug Eo, Byung-Yong Rhim, Koanhoi Kim

Affiliations

  1. Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, Korea.
  2. College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan 54596, Korea.

PMID: 26557022 PMCID: PMC4637358 DOI: 10.4196/kjpp.2015.19.6.549

Abstract

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors/PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

Keywords: CCL11; Secretory phenotype; Signaling pathway; Thrombin; Vascular smooth muscle cell

References

  1. Br J Pharmacol. 1999 Apr;126(8):1735-40 - PubMed
  2. Cell Signal. 1996 Jan;8(1):59-66 - PubMed
  3. Thromb Haemost. 2007 May;97(5):730-7 - PubMed
  4. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9208-12 - PubMed
  5. Thromb Res. 2002 Sep 1;107(5):271-6 - PubMed
  6. Hypertension. 2003 Dec;42(6):1075-81 - PubMed
  7. Pharmacol Rev. 2001 Jun;53(2):245-82 - PubMed
  8. Leukemia. 2003 Jul;17(7):1263-93 - PubMed
  9. J Biol Chem. 1996 Sep 20;271(38):23512-9 - PubMed
  10. J Clin Invest. 1992 Oct;90(4):1614-21 - PubMed
  11. Cancer Treat Rev. 2004 Apr;30(2):193-204 - PubMed
  12. Am J Pathol. 1998 Jul;153(1):81-90 - PubMed
  13. Cytokine Growth Factor Rev. 1999 Mar;10(1):61-86 - PubMed
  14. Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H873-85 - PubMed
  15. Br J Pharmacol. 2001 Apr;132(7):1441-6 - PubMed
  16. J Biol Chem. 1989 Jul 5;264(19):11117-21 - PubMed
  17. Thromb Haemost. 2010 May;103(5):884-90 - PubMed
  18. Biochem Biophys Res Commun. 2010 Jun 4;396(3):748-54 - PubMed
  19. Nature. 2000 Sep 14;407(6801):258-64 - PubMed
  20. Thromb Res. 2008;123(2):288-97 - PubMed
  21. J Mol Cell Cardiol. 2004 Jan;36(1):49-56 - PubMed
  22. Mol Pharmacol. 2005 Jan;67(1):2-11 - PubMed
  23. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1909-19 - PubMed
  24. Cell. 1991 Mar 22;64(6):1057-68 - PubMed
  25. Circulation. 2000 Oct 31;102(18):2185-9 - PubMed
  26. Biochem Soc Trans. 2002 Apr;30(2):194-200 - PubMed
  27. J Immunol. 2001 Jun 15;166(12):7571-8 - PubMed
  28. Thromb Haemost. 2003 Oct;90(4):704-9 - PubMed
  29. Biochim Biophys Acta. 2007 Aug;1773(8):1263-84 - PubMed
  30. Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1211-6 - PubMed
  31. Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1550-5 - PubMed
  32. J Clin Invest. 1989 Oct;84(4):1096-104 - PubMed

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