Podocyte-specific Overexpression of Human Angiotensin-converting Enzyme 2 Attenuates Diabetic Nephropathy in Mice

Abstract

Angiotensin-converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system (RAS). ACE2 is thought to have a renoprotective effect in diabetic nephropathy because it is capable of degrading profibrotic angiotensin II to potentially protective angiotensin-(1-7). Podocyte death and detachment is a key component of diabetic nephropathy. ACE2 is localized in the podocyte and during a diabetic state, podocyte ACE2 expression is reduced. The purpose of this study was to determine the effects of podocyte-specific ACE2 overexpression on the course of diabetic nephropathy. Diabetes was induced using streptozotocin in transgenic mice with podocyte-specific overexpression of human ACE2. The following parameters were assessed: systolic blood pressure, glomerular filtration rate, urinary albumin excretion, mesangial and glomerular area, and podocyte number. Transgenic diabetic mice showed a significant transient attenuated increase in albuminuria, an attenuated increase in mesangial area, decreased glomerular area, and preserved podocyte number, compared to wildtype diabetic mice. This was independent of a change in blood pressure. This study showed that the podocyte-specific overexpression of human ACE2 attenuates the development of diabetic nephropathy.