title: Caldesmon over-expression in type 1 diabetic nephropathy.
abstract: Substantial evidence supports a genetic susceptibility to develop nephropathy in type 1 diabetes and a key pathogenic role of actin cytoskeleton dysfunction in this complication. We previously reported that many cytoskeletal proteins were either up- or down-regulated in fibroblast cells from type 1 diabetic (T1DM) patients with nephropathy. The gene of one of these proteins, caldesmon, lies in a chromosomal region linked to nephropathy and its promoter region contains a single nucleotide polymorphism that is associated with nephropathy. Hence, we analyzed caldesmon gene and protein expression in cultured fibroblasts from T1DM patients with and without nephropathy and from control subjects. Caldesmon gene was studied in cells cultured under normal glucose levels by quantitative real-time RT-PCR. Caldesmon protein isoforms were quantified both under normal and high glucose conditions by two-dimensional electrophoresis. Caldesmon gene was over-expressed in fibroblasts from diabetic patients with nephropathy, in comparison to both those from diabetic patients without nephropathy and those from controls. We quantified six caldesmon protein isoforms, two of them were increased whereas another one was decreased only in fibroblasts from diabetic patients with nephropathy. None of these isoforms showed any difference in their relative abundance in response to high glucose. Variable results in response to high glucose were observed in the expression of other proteins in the three experimental groups. Our data lend further support to an involvement of caldesmon in the susceptibility to diabetic nephropathy in type 1 diabetes, independently from environmental glucose levels.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Millioni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.forename: Livia
authors.initials: L
authors.lastname: Lenzini
authors.forename: Lucia
authors.initials: L
authors.lastname: Puricelli
authors.forename: Brasilina
authors.initials: B
authors.lastname: Caroccia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Tessari
mesh_terms: D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002148:Calmodulin-Binding Proteins; D020033:Protein Isoforms; D005947:Glucose