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  Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice.

Menne, J., Park, J. K., Boehne, M., Elger, M., Lindschau, C., Kirsch, T., et al. (2004). Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice. Diabetes, 53(8), 2101-2109. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15277392.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-ECA3-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-DA8B-0
Genre: Journal Article

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 Creators:
Menne, J., Author
Park, J. K., Author
Boehne, M., Author
Elger, M., Author
Lindschau, C., Author
Kirsch, T., Author
Meier, M., Author
Gueler, F., Author
Fiebeler, A., Author
Bahlmann, F. H., Author
Leitges, M.1, Author              
Haller, H., Author
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Albuminuria/urine; Animals; Base Sequence; Blood Glucose/metabolism; Body Weight; DNA Primers; Diabetes Mellitus, Experimental/blood/genetics/urine; Diabetic Nephropathies/genetics/pathology/urine; Hyperglycemia/genetics/physiopathology; Kidney/anatomy and histology/pathology/ultrastructure; Kidney Glomerulus/anatomy and histology; Mice; Mice, Inbred Strains; Mice, Knockout; Organ Size; Protein Kinase C/deficiency/genetics; Proteoglycans/metabolism; Research Support, Non-U.S. Gov't; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A/blood/genetics; Vascular Endothelial Growth Factor Receptor-2/genetics
 Abstract: Activation of protein kinase C (PKC) isoforms has been implicated in the pathogenesis of diabetic nephropathy. We showed earlier that PKC-alpha is activated in the kidneys of hyperglycemic animals. We now used PKC-alpha(-/-) mice to test the hypothesis that this PKC isoform mediates streptozotocin-induced diabetic nephropathy. We observed that renal and glomerular hypertrophy was similar in diabetic wild-type and PKC-alpha(-/-) mice. However, the development of albuminuria was almost absent in the diabetic PKC-alpha(-/-) mice. The hyperglycemia-induced downregulation of the negatively charged basement membrane heparan sulfate proteoglycan perlecan was completely prevented in the PKC-alpha(-/-) mice, compared with controls. We then asked whether transforming growth factor-beta1 (TGF-beta1) and/or vascular endothelial growth factor (VEGF) is implicated in the PKC-alpha-mediated changes in the basement membrane. The hyperglycemia-induced expression of VEGF165 and its receptor VEGF receptor II (flk-1) was ameliorated in PKC-alpha(-/-) mice, whereas expression of TGF-beta1 was not affected by the lack of PKC-alpha. Our findings indicate that two important features of diabetic nephropathy-glomerular hypertrophy and albuminuria-are differentially regulated. The glucose-induced albuminuria seems to be mediated by PKC-alpha via downregulation of proteoglycans in the basement membrane and regulation of VEGF expression. Therefore, PKC-alpha is a possible therapeutic target for the prevention of diabetic albuminuria.

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Language(s): eng - English
 Dates: 2004-08
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Diabetes
Source Genre: Journal
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Pages: - Volume / Issue: 53 (8) Sequence Number: - Start / End Page: 2101 - 2109 Identifier: -