Blockade of myeloid differentiation 2 attenuates diabetic nephropathy by reducing activation of the renin-angiotensin system in mouse kidneys.

ABSTRACT:

Background and purpose

Both innate immunity and the renin-angiotensin system (RAS) play important roles in the pathogenesis of diabetic nephropathy (DN). Myeloid differentiation factor 2 (MD2) is a co-receptor of toll-like receptor 4 (TLR4) in innate immunity. While TLR4 is involved in the development of DN, the role of MD2 in DN has not been characterized. It also remains unclear whether the MD2/TLR4 signalling pathway is associated with RAS activation in diabetes.

Experimental approach

MD2 was blocked using siRNA or the low MW inhibitor, L6H9, in renal proximal tubular cells (NRK-52E cells) exposed to high concentrations of glucose (HG). In vivo, C57BL/6 and MD2^-/- mice were injected with streptozotocin to induce Type 1 diabetes and nephropathy.

Key results</

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6592858 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature