Emodin upregulates urokinase plasminogen activator, plasminogen activator inhibitor-1 and promotes wound healing in human fibroblasts.
Urokinase plasminogen activator (uPA) system is important for several biological processes that call for extracellular proteolysis, fibrinolysis, cell migration, proliferation and angiogenesis. The current study highlights the fibrinolytic and wound healing potential of emodin, an anthraquinone, with relevance to the uPA system. Emodin increased the fibrinolytic activity of fibroblast cells in a dose-dependent manner. Zymography linked the activity to increased uPA activity. Subsequent RT-PCR and western analyses demonstrated uPA gene upregulation. Interestingly, PAI-1, the inhibitor of uPA was also upregulated. EMSA showed the upregulation occurred independent of emodin's effect on nuclear factor kappa B (NFkappaB). The effect on uPA system is supposedly via generation of reactive oxygen species (ROS) since cotreatment with ascorbic acid, an anti-oxidant, attenuated the activity. In addition to profibrinolytic potential, emodin also demonstrated wound healing activity in in vitro wound models. Presence of emodin in the medium enhanced the rate of migration of fibroblasts into the wounded region. These in vitro experiments reveal that emodin is a potent profibrinolytic and wound healing agent.
Radha
K S
KS
Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
Madhyastha
H K
HK
Nakajima
Y
Y
Omura
S
S
Maruyama
M
M
D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004642:Emodin / Q000494:pharmacology*; D005337:Fibrin / Q000032:analysis / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013778:Tetrazolium Salts; D013844:Thiazoles; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*; D014945:Wound Healing / Q000187:drug effects*
D000975:Antioxidants; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D047428:Protein Kinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D005337:Fibrin; D004247:DNA; D007770:L-Lactate Dehydrogenase; D014568:Urokinase-Type Plasminogen Activator; C022616:thiazolyl blue; D004642:Emodin