title: Altered chaperone and protein turnover regulators expression in cultured skin fibroblasts from type 1 diabetes mellitus with nephropathy.
abstract: In type-1 diabetes mellitus (T1DM) with diabetic nephropathy (DN), accumulation of abnormal proteins in the kidney and other tissues may derive from constitutive alterations of intracellular protein recognition, assembly, and turnover. We characterized the proteins involved in these functions in cultured skin fibroblasts from long-term T1DM patients with [DN+] or without [DN-] nephropathy but similar metabolic control, and from matched healthy subjects. 2-D gel electrophoresis and MS-MALDI analysis were employed. The [DN+] T1DM patients, compared with the two other groups, exhibited increased abundance of a high-molecular weight isoform of protein disulphide-isomerase A3 and a decrease of two low-molecular weight isoforms. They also had increased levels of heat shock protein (HSP) 60 kDa isoform #A4, of HSP71 kDa isoform #A30, and of HSP27 kDa isoform #6, whereas the HSP27 kDa isoforms #A90 and #A71 were decreased. Cathepsin beta-2 (#40), the cation-independent mannose 6-phosphate receptor binding protein 1 (CIMPR) (#A27), and annexin 2 (#A9) were also decreased in the [DN+] T1DM patients, whereas the RNA-binding protein regulatory subunity (#38) and the translationally-controlled tumor protein (TCTP) (#A45) were increased. These changes of chaperone-like proteins in fibroblasts may highlight those of the kidney and be patho-physiologically related to the development of nephropathy in T1DM.
authors.affiliation: Department of Clinical and Experimental Medicine, Chair of Metabolism, University of Padova, Padova, Italy. paolo.tessari@unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Tessari
authors.forename: Lucia
authors.initials: L
authors.lastname: Puricelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Monica
authors.initials: M
authors.lastname: Vedovato
authors.forename: Peter
authors.initials: P
authors.lastname: James
authors.forename: Anna
authors.initials: A
authors.lastname: Coracina
authors.forename: Renato
authors.initials: R
authors.lastname: Millioni
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000737:chemistry* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D018832:Molecular Chaperones / Q000032:analysis*; D019704:Protein Disulfide-Isomerases / Q000032:analysis; D017510:Protein Folding; D011506:Proteins / Q000032:analysis*; D012867:Skin / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human