Hyperhexosemia Induced Functional and Structural Changes in the Kidneys: Role of Endothelins

Vol. 90, No. 1, 2002

Free Abstract Article (Fulltext) Article (PDF 655 KB)

Original Paper

Hyperhexosemia Induced Functional and Structural Changes in the Kidneys: Role of Endothelins
S. Chen, T. Evans, D. Deng, M. Cukiernik, S. Chakrabarti

Department of Pathology, University of Western Ontario, London, Ontario, Canada

Address of Corresponding Author

Nephron 2002;90:86-94 (DOI: 10.1159/000046319)

Key Words

Endothelins
Hyperhexosemia
Kidney
Bosentan
Basement membrane

Abstract

Background/Aims: Glomerular basement membrane (GBM) thickening and mesangial matrix expansion are characteristic features of diabetic nephropathy. The present study investigates the role of endothelins (ETs) in the pathogenesis of such changes in diabetic nephropathy. Methods: Diabetic (streptozotocin-induced, 65 mg/kg), galactose-fed (30%) and control animals were followed up for 1 and 6 months. Animal groups also included diabetic and galactose fed animals on dual ET_A/ET_B receptor antagonist bosentan (100 mg/kg). A semi-quantitative reverse transcription polymerase chain reaction method was used to quantify mRNA expression of ET-1, ET-3, ET_A, ET_B, fibronectin and collagen alpha 2(IV). Histological analyses of the kidneys and ET-1, ET-3 and fibronectin immunohistochemistry were performed. Morphometric assessment of the GBM after 6 months was performed. Results: Diabetes increased mRNA expression of ET-1, ET-3, ET_A, ET_B, fibronectin and collagen alpha 2(IV) after one and six months. In contrast, although increased ET_A and ET_B mRNAs were present following galactose feeding both at 1 and 6 months, ET-1, ET-3, fibronectin and collagen alpha 2(IV)mRNAs were increased after 6 months. Both diabetes and galactose feeding caused increased GBM thickening. Furthermore, diabetes caused an increase in mesangial matrix production. Bosentan prevented increased fibronectin and collagen alpha 2(IV) mRNA expression, increased mesangial matrix deposition and GBM thickening. Conclusion: This study has demonstrated that diabetes and galactose feeding induced functional and structural changes in the kidney are mediated via ETs.

Author Contacts

Subrata Chakrabarti
Department of Pathology, University of Western Ontario
London, Ont. N6A 5A5 (Canada)
Tel. +1 519 663 3381, Fax +1 519 663 2930
E-Mail schakrab@julian.uwo.ca

Article Information

Accepted: March 27, 2001
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 0, Number of References : 45

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