Podoplanin hetero-insufficiency demonstrates congenital protein-losing enteropathy by inflammation in the jejunum: NO synthase inhibitor may become a selective tool for pharmacological therapy

Abstract

We demonstrated that podoplanin was expressed in jejunal villi. Based on the finding, we aimed to clarify the pathogenesis of congenital protein-losing enteropathy (PLE) using podoplanin heterozygeous knock-out (Pdpn-het KO) mice and aspirin-mediated inflammation of the jejunum. Podoplanin was expressed with differential region of the jejunal villi in the Pdpn-het KO mice compared with wild-type one. Fluorescent intensity of intravenous administration of FITC-albumin in the jejunal villi of Pdpn-het KO mice was significantly greater than that of wild-type mice. In the wild-type mice, the blue-colored mesenteric lymph vessels and lymph nodes were observed around 6 min after intravenous injection of Evans blue dye. However, in the Pdpn-het KO mice, the blue-colored lymph vessel and lymph nodes were not observed until 15 min. In the Pdpn-het KO mice, aspirin-mediated jejunal inflammation leaked significantly the intravenous administration of FITC-albumin into the jejunal canal. To design pharmacological therapy for PLE, the effects of N^G-Nitro-L-arginine methyl ester hydrochloride (L-NAME) on permeant albumin in jejunal villi were investigated. Pretreatment with L-NAME significantly reduced the intravenous administration of FITC-albumin distribution in the jejunal villi of Pdpn-het KO mice. In conclusion, we proposed that Podoplanin hetero-insufficiency with jejunal inflammation causes the pathogenesis of congenital PLE. The NO synthase inhibitor may become pharmacological tool for the therapy of PLE.