title: Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes.
abstract: Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B(2)-receptors (B(2)R) in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B(2)R knockout (B(2)R(-/-)) mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER) were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B(2)R(-/-)D null mice had a significantly decreased AER levels compared to wild type B(2)R(+/+)D mice (P = 0.0005). Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B(2)R(+/+)C, B(2)R(+/+)D, B(2)R(-/-)C and B(2)R(-/-)D) highlighted the role of several altered pathological pathways in response to disruption of B(2)R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN.
authors.affiliation: Epidemiology and Population Health Department, Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon.
authors.forename: Miran A
authors.initials: MA
authors.lastname: Jaffa
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.forename: Moustafa
authors.initials: M
authors.lastname: Al Hariri
authors.forename: Hussein
authors.initials: H
authors.lastname: Chalhoub
authors.forename: Assaad
authors.initials: A
authors.lastname: Eid
authors.forename: Fuad N
authors.initials: FN
authors.lastname: Ziyadeh
authors.forename: Ayad A
authors.initials: AA
authors.lastname: Jaffa
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020869:Gene Expression Profiling / Q000379:methods*; D005919:Glomerular Filtration Rate / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D043782:Receptor, Bradykinin B2 / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D001786:Blood Glucose; D043782:Receptor, Bradykinin B2