Circulating antibodies to nephrin in patients with type 1 diabetes.

Background: Patients with type 1 diabetes typically develop autoantibodies to antigens of the pancreatic islet cells including insulin, glutamic acid decarboxylase and the protein tyrosine phosphatase-related islet antigen 2 protein. Nephrin is a protein shared by the kidney glomeruli, pancreatic beta-cells and islet microendothelia. Since circulating antibodies to nephrin have been shown to cause proteinuria, we wanted to test whether such autoantibodies can be detected in diabetic patients.

Nephrin loss in experimental diabetic nephropathy is prevented by deletion of protein kinase C alpha signaling in-vivo.

Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of negative charges in the basement membrane, and changes a of the slit-membrane diaphragm composition. We have recently shown that protein kinase C alpha (PKCalpha)-deficient mice are protected against the development of albuminuria under diabetic conditions. We here tested the hypothesis that PKCalpha mediates the hyperglycemia-induced downregulation of the slit-diaphragm protein nephrin.

Podocyte-associated proteins FAT, alpha-actinin-4 and filtrin are expressed in Langerhans islets of the pancreas.

Nephrin is a crucial podocyte molecule in the kidney glomerular filtration barrier and it is also expressed in Langerhans islet beta cells of the pancreas. Recently, genetic mapping of proteinuric kidney disease genes and animal models have revealed further important molecules for the kidney filtration function including alpha-actinin-4, podocin, FAT, and NEPH1. This study was addressed to explore the pancreatic expression of the podocyte molecules podocin, FAT, alpha-actinin-4, NEPH1, NEPH2, filtrin/NEPH3, synaptopodin and CD2 associated protein (CD2AP).

Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes.

Background And Aim: The development of autoantibodies against antigens of the pancreatic islet cells is a typical phenomenon in patients with type 1 diabetes. The expression of densin, recently shown to be present in kidney podocytes, was explored in the pancreas. Additionally, we studied whether densin and filtrin, another molecule shared between the kidney podocytes and pancreatic islet cells, can act as autoantigens and whether autoantibodies against these can be detected in patients with type 1 diabetes.

Nephrin in human lymphoid tissues.

When nephrin, the protein product of NPHS1, was cloned, it was proposed to be specific for the kidney glomerular podocytes. Recently, however, new reports have emerged verifying additional nephrin expression sites, particularly the insulin-producing beta cells of the pancreas, as well as the central nervous system. In this study, we demonstrate nephrin expression in lymphoid tissues, specifically the tonsil, adenoid and lymph node.