Protein Kinase C β Inhibition Attenuates the Progression of Experimental Diabetic Nephropathy in the Presence of Continued Hypertension
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- Darren J. Kelly
- Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
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- Yuan Zhang
- Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
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- Claire Hepper
- Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
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- Renae M. Gow
- Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
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- Kassie Jaworski
- Department of Physiology, University of Melbourne, Parkville, Victoria, Australia
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- Bruce E. Kemp
- St. Vincent’s Institute of Medical Research, Fitzroy, Victoria, Australia
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- Jennifer L. Wilkinson-Berka
- Department of Physiology, University of Melbourne, Parkville, Victoria, Australia
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- Richard E. Gilbert
- Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria, Australia
抄録
<jats:p>In addition to hyperglycemia, hypertension and the renin-angiotensin system have been consistently implicated in the pathogenesis of diabetic nephropathy. Each of these pathogenetic factors may induce changes in cellular function by a common intracellular signaling pathway, the activation of protein kinase C (PKC) β. The present study thus sought to determine the in vivo effect of PKC β inhibition in experimental diabetic nephropathy in the setting of continued hyperglycemia, hypertension, and activation of the RAS. Studies were conducted in the (mRen-2)27 rat, a rodent that is transgenic for the entire mouse renin gene (Ren-2) and develops many of the structural, functional, and molecular characteristics of human diabetic nephropathy when experimental diabetes is induced with streptozotocin (STZ). Six-week-old female Ren-2 rats received an injection of STZ or vehicle and were maintained for 6 months. Within 24 h, diabetic rats were further randomized to receive treatment with the specific PKC β inhibitor, LY333531, admixed in diet (10 mg · kg−1 · d−1) or no treatment (n = 8/group). Diabetic rats developed albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis with a concomitant increase in transforming growth factor-β (TGF-β). Western blot analysis demonstrated increased PKC β in diabetic animals, localized by immunofluorescence to the glomerular mesangium. In vivo inhibition of PKC β with LY333531 led to a reduction in albuminuria, structural injury, and TGF-β expression, despite continued hypertension and hyperglycemia.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 52 (2), 512-518, 2003-02-01
American Diabetes Association
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詳細情報
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- CRID
- 1363670318258454912
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- NII論文ID
- 30026274812
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- ISSN
- 1939327X
- 00121797
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- データソース種別
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- Crossref
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