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.

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.

Molecular cloning and characterization of an endogenous antisense transcript of Nphs1.

Mutations of NPHS1, the gene encoding the kidney glomerular filtration barrier protein nephrin, cause congenital nephrotic syndrome of the Finnish type. Nephrin is a component of the interpodocyte-spanning slit diaphragm: it mediates outside-in signaling and forms a nexus for homo- and heterotypic molecular interactions. When studying the nephrin-deficient mouse line generated by random insertional mutagenesis we unexpectedly discovered an endogenous antisense transcript originating from the nephrin-encoding locus.