PMID- 20607592 OWN - NLM STAT- MEDLINE DCOM- 20110310 LR - 20211020 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 344 IP - 1-2 DP - 2010 Nov TI - Protein kinase Cdelta mediates MCP-1 mRNA stabilization in vascular smooth muscle cells. PG - 73-9 LID - 10.1007/s11010-010-0530-6 [doi] AB - Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine that promotes atherosclerosis and is a mediator of the response to arterial injury. We previously demonstrated that platelet-derived growth factor (PDGF) and angiotensin II (Ang) induce the accumulation of MCP-1 mRNA in vascular smooth muscle cells mainly by increasing mRNA stability. In the present study, we have examined the signaling pathways involved in this stabilization of MCP-1 mRNA. The effect of PDGF (BB isoform) and Ang on MCP-1 mRNA stability was mediated by the PDGF beta and angiotensin II receptor AT1R, respectively, and did not involve transactivation between the two receptors. The effect of PDGF-BB was blocked by inhibitors of protein kinase C (PKC), but not by inhibitors of phosphoinositol 3-kinase (PI3K), Src, or NADPH oxidase (NADPHox). In contrast, the effect of Ang was blocked by inhibitors of Src, and PKC, but not by inhibitors of PI3 K, or NADPHox. The effect of PDGF BB on MCP-1 mRNA stability was blocked by siRNA directed against PKCdelta and protein kinase D (PKD), whereas the effect of Ang was blocked only by siRNA directed against PKCdelta. These results suggest that the enhancement of MCP-1 mRNA stability by PDGF-BB and Ang are mediated by distinct "proximal" signaling pathways that converge on activation of PKCdelta. This study identifies a novel role for PKCdelta in mediating mRNA stability in smooth muscle cells. FAU - Liu, Bin AU - Liu B AD - Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Bin_liu@urmc.rochester.edu FAU - Dhawan, Latika AU - Dhawan L FAU - Blaxall, Burns C AU - Blaxall BC FAU - Taubman, Mark B AU - Taubman MB LA - eng GR - P01 HL77789/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100704 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - EC 2.7.11.13 (Protein Kinase C-delta) SB - IM MH - Animals MH - Blotting, Western MH - Chemokine CCL2/*genetics MH - Male MH - Muscle, Smooth, Vascular/cytology/*enzymology MH - Protein Kinase C-delta/*metabolism MH - RNA, Messenger/*genetics MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction MH - Transcriptional Activation EDAT- 2010/07/08 06:00 MHDA- 2011/03/11 06:00 CRDT- 2010/07/08 06:00 PHST- 2010/01/11 00:00 [received] PHST- 2010/06/22 00:00 [accepted] PHST- 2010/07/08 06:00 [entrez] PHST- 2010/07/08 06:00 [pubmed] PHST- 2011/03/11 06:00 [medline] AID - 10.1007/s11010-010-0530-6 [doi] PST - ppublish SO - Mol Cell Biochem. 2010 Nov;344(1-2):73-9. doi: 10.1007/s11010-010-0530-6. Epub 2010 Jul 4.