Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy

Tim Fugmann, Beatrice Borgia, Csaba Révész, Mária Godó, Carol Forsblom, P. Hamar, Harry Holthöfer, Dario Neri, Christoph Roesli

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

At present, the urinary albumin excretion rate is the best noninvasive predictor for diabetic nephropathy (DN) but major limitations are associated with this marker. Here, we used in vivo perfusion technology to establish disease progression markers in an animal model of DN. Rats were perfused with a reactive ester derivative of biotin at various times after streptozotocin treatment. Following homogenization of kidney tissue and affinity purification of biotinylated proteins, a label-free mass spectrometry-based proteomic analysis of tryptic digests identified and relatively quantified 396 proteins. Of these proteins, 24 and 11 were found to be more than 10-fold up-or downregulated, respectively, compared with the same procedure in vehicle-treated rats. Changes in the expression of selected differentially regulated proteins were validated by immunofluorescence detection in kidney tissue from control and diabetic rats. Immunoblot analysis of pooled human urine found that concentrations of vanin-1, an ectoenzyme pantetheinase, distinguished diabetic patients with macroalbuminuria from those with normal albuminuria. Uromodulin was elevated in the urine pools of the diabetic patients, regardless of the degree of albuminuria, compared with healthy controls. Thus, in vivo biotinylation facilitates the detection of disease-specific changes in the abundance of potential biomarker proteins for disease monitoring and/or pharmacodelivery applications.

Original languageEnglish
Pages (from-to)272-281
Number of pages10
JournalKidney International
Volume80
Issue number3
DOIs
Publication statusPublished - Aug 1 2011

Fingerprint

Diabetic Nephropathies
Proteomics
Kidney
Albuminuria
Proteins
Uromodulin
Urine
Biotinylation
Streptozocin
Biotin
Fluorescent Antibody Technique
Disease Progression
Albumins
Mass Spectrometry
Esters
Down-Regulation
Animal Models
Perfusion
Biomarkers
Technology

Keywords

  • diabetic nephropathy
  • diagnosis
  • podocyte
  • vascular access

ASJC Scopus subject areas

  • Nephrology

Cite this

Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. / Fugmann, Tim; Borgia, Beatrice; Révész, Csaba; Godó, Mária; Forsblom, Carol; Hamar, P.; Holthöfer, Harry; Neri, Dario; Roesli, Christoph.

In: Kidney International, Vol. 80, No. 3, 01.08.2011, p. 272-281.

Research output: Contribution to journalArticle

Fugmann, T, Borgia, B, Révész, C, Godó, M, Forsblom, C, Hamar, P, Holthöfer, H, Neri, D & Roesli, C 2011, 'Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy', Kidney International, vol. 80, no. 3, pp. 272-281. https://doi.org/10.1038/ki.2011.116
Fugmann, Tim ; Borgia, Beatrice ; Révész, Csaba ; Godó, Mária ; Forsblom, Carol ; Hamar, P. ; Holthöfer, Harry ; Neri, Dario ; Roesli, Christoph. / Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy. In: Kidney International. 2011 ; Vol. 80, No. 3. pp. 272-281.
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