Deficiency of ACE2 (angiotensin-converting enzyme 2), which degrades Ang (angiotensin) II, promotes the development of glomerular lesions. However, the mechanisms explaining why the reduction in ACE2 is associated with the development of glomerular lesions have still to be fully clarified. We hypothesized that ACE2 may regulate the renoprotective actions of ANP (atrial natriuretic peptide). The aim of the present study was to investigate the effect of ACE2 deficiency on the renal production of ANP. We evaluated molecular and structural abnormalities, as well as the expression of ANP in the kidneys of ACE2-deficient mice and C57BL/6 mice. We also exposed renal tubular cells to AngII and Ang-(1-7) in the presence and absence of inhibitors and agonists of RAS (renin-angiotensin system) signalling. ACE2 deficiency resulted in increased oxidative stress, as well as pro-inflammatory and profibrotic changes. This was associated with a down-regulation of the gene and protein expression on the renal production of ANP. Consistent with a role for the ACE2 pathway in modulating ANP, exposing cells to either Ang-(1-7) or ACE2 or the Mas receptor agonist up-regulated ANP gene expression. This work demonstrates that ACE2 regulates renal ANP via the generation of Ang-(1-7). This is a new mechanism whereby ACE2 counterbalances the renal effects of AngII and which explains why targeting ACE2 may be a promising strategy against kidney diseases, including diabetic nephropathy.
Aims/hypothesis Coeliac disease is common in type 1 diabetes. It is managed with a gluten-free diet, characterised by foods low in AGEs. We hypothesised that this diet would lead to lower plasma AGEs and be associated with reduced albuminuria. Methods From a single paediatric clinic, we recruited 21 children with type 1 diabetes and biopsy-proven coeliac disease, and 38 individuals with diabetes alone. The groups were matched for age, sex, duration of disease and metabolic control. Participants completed a detailed clinical and dietary history. Blood samples were taken for HbA 1c , coeliac serology, thyroid function, serum IgA levels and plasma AGEs, and urine samples were obtained for estimation of the albumin/creatinine ratio (ACR).
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