Induction of angiogenesis by hepatocyte growth factor and nitric oxide in periodontitis

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Hepatocyte growth factor(HGF)is purified in plasma of patients with fulminant hepatic failure as a potent mitogen for parenchymal hepatocytes.However numerous subsequent studies have revealed that HGF has many activities such as angiogenesis activity.The recent studies, in particular, appears promising as a therapeutic agent for chronic obstructive arteriosclerosis and insufficient blood supply in the foot as a consequence of diabetes.By the way, diabetes patients are at greater risk of developing periodontitis, may not respond as well to periodontal therapy as non-diabetic patients.Almost complications due to diabetes are caused by obstruction of micro vessels.In this study we focus on the angiogenesis activity among various activities of HGF, and we examined the involvement of HGF in diabetic periodontitis.At first we examined the effects of reactive oxygen species(ROS)on HGF production because ROS such as super oxide, nitric oxide and peroxynitrite are thought to cause various diabetes complications.We revealed that ROS significantly decreased in HOF production by gingival fibroblasts.This result suggested that ROS production develop diabetes periodontitis mediated an inhibition of the production of HGF as an angiogenesis factor.Next we study the involvement of angiogenesis in HGF and nitric oxide, one of ROS.By the way, branching and elongation of cells are necessary for angiogenesis.Therefore we examined the effect of HGF or nitric oxide on branching of cells, and then we examined the effects of inhibitory agents of signal transduction on branching of cells induced by HGF.We found that HGF and nitric oxide additively stimulated branching of cells and induced cell to cell net-work. Furthermore we revealed that PI3kinase involved in the branching of cells, which involved in matrix metalloprotenases.This study shows that the involvememt of HGF production in the deteriorating of diabetic periodontitis due to decrease in an angiogenetic activity.