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Differential glomerular proteome analysis of two murine nephropathy models at onset of albuminuria
Author(s) -
Blutke Andreas,
Block Carolin,
Berendt Frank,
Herbach Nadja,
Kemter Elisabeth,
Amann Kerstin,
Fröhlich Thomas,
Arnold Georg J.,
Wanke Ruediger
Publication year - 2011
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201000103
Subject(s) - albuminuria , glomerulosclerosis , diabetic nephropathy , endocrinology , medicine , nephropathy , focal segmental glomerulosclerosis , glomerular basement membrane , biology , muscle hypertrophy , proteinuria , kidney , diabetes mellitus
Purpose : Early stages of various entities of progressive kidney diseases are commonly characterized by development of glomerular hypertrophy and albuminuria. The purpose of the present study was to identify protein biomarker candidates for these glomerular alterations. Experimental design : Quantitative differences in the glomerular proteomes of two unrelated murine nephropathy models in the defined stage of glomerular hypertrophy at onset of albuminuria were identified by 2‐D DIGE and MALDI‐TOF/TOF analysis. Investigated mouse models were (I): transgenic (tg) mice expressing a dominant negative glucose‐dependent insulinotropic polypeptide receptor (GIPR dn ), a model of diabetes mellitus associated nephropathy and (II): growth hormone (GH)‐tg mice, an established model of progressive glomerulosclerosis. Results : In GIPR dn ‐tg mice, nine differentially abundant glomerular proteins were unambiguously identified, and eight in GH‐tg mice (each versus controls). Four proteins (Annexin A4, Dihydropyrimidinase‐related protein 2, Myosin regulatory light chain 2, Tropomyosin 1) displayed a congeneric differential glomerular abundance in both models, thus representing a common differential protein expression profile of glomerular hypertrophy at onset of albuminuria. The glomerular presence of these proteins was also detected in specimen of human focal and segmental glomerulosclerosis and diabetic nephropathy. Conclusions and clinical relevance : Our findings suggest a pathogenetic relevance of the identified proteins in early stages of chronic kidney diseases and their potential use as diagnostic markers.