title: Downregulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 by grape seed proanthocyanidin extract.
abstract: Urokinase plasminogen activator (uPA) system, comprising of uPA, its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor (PAI-1), plays a vital role in various biological processes involving extracellular proteolysis, fibrinolysis, cell migration and proliferation. The timely occurence of these processes are essential for normal wound healing. This study examines the regulation of uPA and PAI-1 by a natural polyphenol-rich compound, grape seed extract (GSE). GSE is reported to have beneficial effects in promoting wound healing. Fibroblast cells exposed to different doses of GSE for 18hours were processed for further studies such as ELISA, RT-PCR, western blotting, fibrinolytic assay, cell surface plasmin activity assay and in vitro wound healing assay. GSE treatment caused a significant downregulation of uPA and PAI-1 expression, both at the RNA and protein levels. ELISA also revealed a dose-dependent decrease in uPA and PAI-1 activities. Functional significance of the downregulation was evident in decreased fibrinolytic activity, concomittant with decreased cell-surface plasmin activity. In vitro wound healing studies showed that GSE also retarded the migration of cells towards the wounded region.
authors.affiliation: Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Dhungana
authors.initials: D
authors.lastname: Sandra
authors.forename: Madhyastha
authors.initials: M
authors.lastname: Radha
authors.forename: Madhyastha
authors.initials: M
authors.lastname: Harishkumar
authors.forename: Nakajima
authors.initials: N
authors.lastname: Yuichi
authors.forename: Omura
authors.initials: O
authors.lastname: Sayuri
authors.forename: Maruyama
authors.initials: M
authors.lastname: Masugi
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D010636:Phenols / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D059808:Polyphenols; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012639:Seeds; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D056604:Grape Seed Extract; D010636:Phenols; D017395:Plasminogen Activator Inhibitor 1; D059808:Polyphenols; D044945:Proanthocyanidins; D012333:RNA, Messenger; C013221:proanthocyanidin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator