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Abnormal cytoskeletal protein expression in cultured skin fibroblasts form type 1 diabetes mellitus patiens with nephropathy: A proteomic approach

Author:
  • R. Millioni
  • E. Lori
  • L. Puricelli
  • Giorgio Arrigoni
  • M. Vedovato
  • R. Trevisan
  • Peter James
  • A. Tiengo
  • P. Tessari
Publishing year: 2008
Language: English
Pages: 492-503
Publication/Series: Proteomics Clinical Applications
Volume: 2
Issue: 4
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

Diabetic nephropathy (DN) develops in about 40% of insulin-dependent type 1 diabetes mellitus (TlDM) patients, and is associated not only with diabetes duration and metabolic control, but also with a genetic predisposition. Constitutive alterations of cytoskeletal proteins may play a role in the development of DN. We investigated the expression of these proteins in cultured skin fibroblasts, obtained from long-term TlDM patients with and without DN but comparable metabolic control, and from matched healthy subjects, by means of 2-DE electrophoresis and MS-MALDI analyses. In T1DM with DN, compared to the other two groups, quantitative analyses revealed an altered expression of 17 spots (p < 0.05-p < 0.01), corresponding to 12 unique proteins. In T1DM with DN, beta-actin and three isoforms of tubulin beta-2 chain, tropomodulin-3, and LASP-1 were decreased, whereas two tubulin beta-4 chain isoforms, one alpha actinin4 isoform, membrane-organizing extension spike protein (MOESIN), FLJ00279 (corresponding to a fragment of myosin heavy chain, non-muscle type A), vinculin, a tropomyosin isoform, and the macrophage capping protein were increased. A shift in caldesmon isoforms was also detected. These results demonstrate an association between DN and the constitutive expression of cytoskeleton proteins in cultured skin fibroblasts from TlDM with DN, which may retain pathophysiologycal implications.

Keywords

  • Cell and Molecular Biology
  • IDDM PATIENTS
  • ACTIN POLYMERIZATION
  • ANTIPORT ACTIVITY
  • cytoskeletal proteins
  • PHENOTYPE
  • ASSIGNMENT
  • MICROALBUMINURIA
  • INSULIN
  • ERM PROTEINS
  • MESANGIAL CELLS
  • GENE-EXPRESSION
  • diabetic nephropathy
  • fibroblasts

Other

Published
  • ISSN: 1862-8354
Peter James
E-mail: peter.james [at] immun.lth.se

Professor

Department of Immunotechnology

+46 46 222 14 96

+46 70 247 79 60

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