MASP‐2 deficiency does not prevent the progression of diabetic kidney disease in a mouse model of type 1 diabetes

Abstract

AbstractMannan‐binding lectin (MBL) initiates the lectin pathway of complement and has been linked to albuminuria and mortality in diabetes. We hypothesize that MBL‐associated serine protease 2 (MASP‐2) deficiency will protect against diabetes‐induced kidney damage. Male C57BL/6J MASP‐2 knockout (Masp2−/−) mice and wildtype (WT) mice were divided into a diabetic group and a non‐diabetic group. Renal hypertrophy, albumin excretion, mesangial area and specific mRNA expressions in the renal cortex were measured after 8 and 12 weeks of diabetes. By two‐way ANOVA it was tested if MASP‐2 modulated the renal effects of diabetes, that is interaction. After 12 weeks of diabetes Masp2−/− diabetic mice had a smaller mesangium at 21.1% of the glomerular area (95% CI 19.7, 22.6) compared with WT diabetic mice, 25.2% (23.2, 27.2), p(interaction) = 0.001. After 8 weeks of diabetes, plasma cystatin C was 261.5 ng/mL (229.6, 297.8) in the WT diabetic group compared to 459.9 ng/mL (385.7, 548.3) in non‐diabetic WT mice, p < 0.001. By contrast, no difference in plasma cystatin C levels was found between the Masp2−/− diabetic mice, 288.2 ng/mL (260.6, 318.6) and Masp2−/− non‐diabetic mice, 293.5 ng/mL (221.0, 389.7), p = 0.86 and p(interaction) = 0.001. We demonstrated a protective effect of MASP‐2 deficiency on mesangial hypertrophy after 12 weeks of diabetes and an effect on plasma cystatin C level. MASP‐2 deficiency did, however, fail to protect against diabetic‐induced alterations of kidney weight, albuminuria and renal mRNA expression of fibrotic‐ and oxidative stress markers.