Macrophages Directly Mediate Diabetic Renal Injury.

Macrophages Directly Mediate Diabetic Renal Injury.
Am J Physiol Renal Physiol. 2013 Oct 30;
Authors: You H, Gao T, Cooper TK, Reeves WB, Awad AS
Abstract
Monocyte/macrophage recruitment correlates strongly with the progression of renal impairment in diabetic nephropathy (DN), yet their direct role is not clear. We hypothesize that macrophages contribute to direct podocyte injury and/or an abnormal podocyte niche leading to DN. Experiments were conducted in CD11b-DTR mice treated with diphtheria toxin (DT) to deplete macrophages following streptozotocin (STZ) induced diabetes. Additional experiments were conducted in bone marrow chimeric (CD11b-DTR→ C57BL6/J) mice. Diabetes was associated with an increase in the M1/M2 ratio by 6 weeks following induction of diabetes. Macrophage depletion in diabetic CD11b-DTR mice significantly attenuated albuminuria, kidney macrophage recruitment, glomerular histologic changes and preserved kidney nephrin and podocin expression compared with diabetic CD11b-DTR mice treated with mutant DT. These data were confirmed in chimeric mice indicating a direct role of bone marrow-derived macrophages in DN. In vitro, podocytes grown in high glucose media significantly increased macrophage migration compared to podocytes grown in normal glucose media. In addition, classically activated M1 macrophages; but not M2 macrophages; induced podocyte permeability. These findings provide evidence that macrophages directly contri...

Source: Am J Physiol Renal P... - October 30, 2013 Category: Urology & Nephrology Authors: You H, Gao T, Cooper TK, Reeves WB, Awad AS Tags: Am J Physiol Renal Physiol Source Type: research