title: Persimmon peel extract attenuates PDGF-BB-induced human aortic smooth muscle cell migration and invasion through inhibition of c-Src activity.
abstract: The unregulated migration and invasion of human aortic smooth muscle cells (HASMCs) into the intima is a crucial step in the development of atherosclerosis. Recently, the oriental persimmon extract (Diospyros kaki Thunb. cv. Fuyu) has been investigated for its anti-atherogenic properties, but the molecular mechanisms involved remain unclear. We investigated the inhibitory effects of persimmon peel and flesh extract on the platelet-derived growth factor (PDGF) BB-induced MMP-1 expression using Western blot, and abnormal migration and invasion of HASMCs using a modified Boyden chamber assay and a wound healing assay. We also evaluated the inhibitory effects of persimmon peel extract on aortic vessel thickening using a rat aortic sprouting assay. Persimmon peel (PPE), but not flesh extract (PFE), inhibited PDGF-BB-induced MMP-1 expression, cell migration and invasion in HASMCs, while suppressing the rat aortic sprouting. Western blot and in vitro kinase assay data demonstrated that PPE inhibited Src kinase activity and subsequently attenuated PDGF-BB-induced phosphorylation of MAPK and Akt signalling pathways. Taken together, our results indicate that persimmon peel might possess a potential anti-atherogenic effect through attenuation of ASMCs migration and invasion and aortic sprouting by direct inhibition of the c-Src kinase activity.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Joe Eun
authors.initials: JE
authors.lastname: Son
authors.forename: Mun Kyung
authors.initials: MK
authors.lastname: Hwang
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Sang Gwon
authors.initials: SG
authors.lastname: Seo
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.forename: Jong Rhan
authors.initials: JR
authors.lastname: Kim
authors.forename: Gwang-Hwan
authors.initials: GH
authors.lastname: Ahn
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D029788:Diospyros / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D016392:Proto-Oncogene Proteins pp60(c-src)
keywords: Aortic smooth muscle cell; Cellular Src; Migration; Persimmon extract; Platelet-derived growth factor