title: Resveratrol inhibits phenotype modulation by platelet derived growth factor-bb in rat aortic smooth muscle cells.
abstract: Dedifferentiated vascular smooth muscle cells (VSMCs) are phenotypically modulated from the contractile state to the active synthetic state in the vessel wall. In this study, we investigated the effects of resveratrol on phenotype modulation by dedifferentiation and the intracellular signal transduction pathways of platelet derived growth factor-bb (PDGF-bb) in rat aortic vascular smooth muscle cells (RAOSMCs). Treatment of RAOSMCs with resveratrol showed dose-dependent inhibition of PDGF-bb-stimulated proliferation. Resveratrol treatment inhibited this phenotype change and disassembly of actin filaments and maintained the expression of contractile phenotype-related proteins such as calponin and smooth muscle actin-alpha in comparison with only PDGF-bb stimulated RAOSMC. Although PDGF stimulation elicited strong and detectable Akt and mTOR phosphorylations lasting for several hours, Akt activation was much weaker when PDGF was used with resveratrol. In contrast, resveratrol only slightly inhibited phosphorylations of 42/44 MAPK and p38 MAPK. In conclusion, RAOSMC dedifferentiation, phenotype, and proliferation rate were inhibited by resveratrol via interruption of the balance of Akt, 42/44MAPK, and p38MAPK pathway activation stimulated by PDGF-bb.
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Byeong-Ju
authors.initials: BJ
authors.lastname: Kwon
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Hyok Jin
authors.initials: HJ
authors.lastname: Seo
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Kyeong Eun
authors.initials: KE
authors.lastname: Yoo
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Koo
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Park
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology*; D000077214:Becaplermin; D054337:Cell Dedifferentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D010641:Phenotype; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000199:Actins; D020574:Proto-Oncogene Proteins c-sis; D013267:Stilbenes; D000077214:Becaplermin; D000077185:Resveratrol
references.citation: Int J Mol Med. 2005 Oct;16(4):533-40
references.pmid: 16142383
references.citation: FEBS Lett. 1999 May 14;451(1):63-7
references.pmid: 10356984
references.citation: J Clin Invest. 1997 Jun 15;99(12):2814-6
references.pmid: 9185501
references.citation: Mol Biol Cell. 2003 Jun;14(6):2482-91
references.pmid: 12808045
references.citation: Physiol Rev. 2004 Jul;84(3):767-801
references.pmid: 15269336
references.citation: Br J Surg. 1994 Sep;81(9):1254-69
references.pmid: 7953384
references.citation: J Cardiovasc Pharmacol. 2007 Jul;50(1):83-93
references.pmid: 17666920
references.citation: Int J Biochem Cell Biol. 2008;40(10):1990-5
references.pmid: 17768079
references.citation: Physiol Rev. 1995 Jul;75(3):487-517
references.pmid: 7624392
references.citation: Life Sci. 1999;64(26):2511-21
references.pmid: 10403511
references.citation: Agents Actions Suppl. 1997;48:3-24
references.pmid: 9177097
references.citation: Ann Biomed Eng. 2005 Nov;33(11):1546-54
references.pmid: 16341922
references.citation: J Lab Clin Med. 1998 Jul;132(1):9-15
references.pmid: 9665366
references.citation: Arterioscler Thromb Vasc Biol. 2002 Dec 1;22(12):1990-5
references.pmid: 12482824
references.citation: J Cell Physiol. 2006 Apr;207(1):123-31
references.pmid: 16270352
references.citation: J Biol Chem. 2001 Sep 7;276(36):33630-7
references.pmid: 11443134
references.citation: Cancer Res. 2000 Jul 1;60(13):3504-13
references.pmid: 10910062
references.citation: Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):795-801
references.pmid: 12637337
references.citation: Semin Interv Cardiol. 1997 Sep;2(3):167-76
references.pmid: 9650223
references.citation: Atherosclerosis. 2009 Jul;205(1):126-34
references.pmid: 19108833
references.citation: Circ Res. 1999 Aug 20;85(4):338-48
references.pmid: 10455062
references.citation: Eur J Pharmacol. 2004 Oct 1;500(1-3):299-313
references.pmid: 15464042
references.citation: Physiol Rev. 1999 Oct;79(4):1283-316
references.pmid: 10508235
references.citation: Hypertension. 2003 Dec;42(6):1075-81
references.pmid: 14581295
references.citation: Circ Res. 2001 Aug 3;89(3):251-8
references.pmid: 11485975
references.citation: J Nutr Biochem. 2013 Nov;24(11):1830-9
references.pmid: 23866995
references.citation: Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1109-15
references.pmid: 17880362
references.citation: Oncogene. 2006 Oct 16;25(48):6347-60
references.pmid: 17041621
references.citation: Science. 1995 Oct 13;270(5234):296-9
references.pmid: 7569979
references.citation: J Cell Physiol. 1990 Mar;142(3):635-42
references.pmid: 2312620
references.citation: J Cardiometab Syndr. 2009 Spring;4(2):102-6
references.pmid: 19614797
references.citation: J Vasc Surg. 2007 Jun;45 Suppl A:A25-32
references.pmid: 17544021
references.citation: Cell. 2006 Feb 10;124(3):471-84
references.pmid: 16469695
references.citation: Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):1152-8
references.pmid: 11451744
references.citation: Horm Res. 1998;50 Suppl 2:15-24
references.pmid: 9721587