Distinct roles of arginases 1 and 2 in diabetic nephropathy

The objective of this study was to identify features of DN that are associated specifically with expression of arginase-1 or –2. Elevated urinary albumin excretion rate and plasma urea levels, increases in renal fibronectin mRNA levels, and decreased renal medullary blood flow were associated almost completely and specifically with arginase-2 expression, indicating that arginase-2 selectively mediates major aspects of diabetic renal injury. However, increases in renal macrophage infiltration and renal TNF-α mRNA levels occurred independent of arginase-2 expression but were almost entirely abolished by treatment with BEC, indicating a distinct role for arginase-1. We therefore generated mice with a macrophage-specific deletion of arginase-1 (CD11bCre/Arg1fl/fl). CD11bCre/Arg1fl/fl mice had significantly reduced macrophage infiltration but had no effect on albuminuria compared with Arg1fl/fl mice after 12 wk of streptozotocin-induced diabetes. These results indicate that selective inhibition of arginase-2 would be effective in preventing or ameliorating major features of diabetic renal injury.

Source: AJP: Renal Physiology - October 1, 2017 Category: Urology & Nephrology Authors: Morris, S. M., You, H., Gao, T., Vacher, J., Cooper, T. K., Awad, A. S. Tags: RESEARCH ARTICLE Source Type: research