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

Charlotte Brinck Holt*, Lene Halkjær, Tom Dudley, Wilhelm Schwaeble, Troels Krarup Hansen, Steffen Thiel, Jakob Appel Østergaard

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Mannan-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.

Original languageEnglish
Article numbere13348
JournalScandinavian Journal of Immunology
Number of pages17
ISSN0300-9475
DOIs
Publication statusPublished - Dec 2023

Keywords

  • MBL-associated serine protease 2
  • complement system
  • diabetic nephropathy
  • lectin pathway

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