Renal effects of a neutralising RAGE-antibody in long term streptozotocin-diabetic mice

Louise J N Jensen, Larry Denner, Bieke F. Schrijvers, Ronald Tilton, Ruth Rasch, Allan Flyvbjerg

Research output: Contribution to journalArticle

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Abstract

Advanced glycation endproducts (AGES) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor mediated pathway and through specific receptors for AGEs (e.g. RAGE). To explore a potentially specific role for RAGE in renal changes in type 1 diabetes, we examined the renal effects of a neutralising murine RAGE-antibody (ab) in streptozotocin (STZ)-diabetic mice, a model of type 1 diabetes. One group of STZ-diabetic mice was treated for two months with the RAGE-ab, while another STZ-diabetic group was treated for the same period with an irrelevant immunoglobulin G (IgG). Two groups of non-diabetic NMRI mice were treated with either RAGE-ab or isotype-matched IgG for two months. Placebo-treated STZ-diabetic mice showed an increase in kidney weight, glomerular volume, basement membrane thickness (BMT), urinary albumin excretion (UAE) and creatinine clearance (CrCl), when compared with non-diabetic controls. In RAGE-ab-treated STZ-diabetic mice, the increase in kidney weight and UAE was reduced, while the increase in CrCl was abolished. RAGE-ab administration in NMRI mice caused a reduction in liver weight and an increase in BMT. Renal messenger RNA (mRNA) for connective tissue growth factor and collagen IVα1 was increased in placebo-treated diabetic animals. RAGE-ab treatment had no impact on the expression of these factors. The renal effects of RAGE-ab administration in STZ-diabetic mice were seen without impact on body weight, blood glucose or food consumption. In conclusion, the present data support the hypothesis that RAGE is an important pathogenic factor in the renal changes in an animal model of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)493-501
Number of pages9
JournalJournal of Endocrinology
Volume188
Issue number3
DOIs
StatePublished - Mar 2006

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Streptozocin
Neutralizing Antibodies
Kidney
Antibodies
Type 1 Diabetes Mellitus
Weights and Measures
Albumins
Creatinine
Immunoglobulin G
Placebos
Connective Tissue Growth Factor
Glomerular Basement Membrane
Diabetic Nephropathies
Basement Membrane
Blood Glucose
Collagen
Animal Models
Body Weight
Food
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology

Cite this

Renal effects of a neutralising RAGE-antibody in long term streptozotocin-diabetic mice. / Jensen, Louise J N; Denner, Larry; Schrijvers, Bieke F.; Tilton, Ronald; Rasch, Ruth; Flyvbjerg, Allan.

In: Journal of Endocrinology, Vol. 188, No. 3, 03.2006, p. 493-501.

Research output: Contribution to journalArticle

Jensen, LJN, Denner, L, Schrijvers, BF, Tilton, R, Rasch, R & Flyvbjerg, A 2006, 'Renal effects of a neutralising RAGE-antibody in long term streptozotocin-diabetic mice', Journal of Endocrinology, vol. 188, no. 3, pp. 493-501. https://doi.org/10.1677/joe.1.06524
Jensen, Louise J N ; Denner, Larry ; Schrijvers, Bieke F. ; Tilton, Ronald ; Rasch, Ruth ; Flyvbjerg, Allan. / Renal effects of a neutralising RAGE-antibody in long term streptozotocin-diabetic mice. In: Journal of Endocrinology. 2006 ; Vol. 188, No. 3. pp. 493-501.
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