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Chymase inhibition retards albuminuria in type 2 diabetes

Benjamin J Bivona1, Shinji Takai2, Dale M Seth3

  • 1Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Physiological Reports
|December 25, 2019
PubMed

Insights

Chronic chymase inhibition slowed the progression of urinary albumin excretion in diabetic mice, suggesting renal chymase contributes to type 2 diabetes kidney disease progression.

Area of Science:

  • Nephrology
  • Endocrinology
  • Biochemistry

Background:

  • Mast cell chymase contributes to pro-fibrotic, inflammatory, and vasoconstrictor processes.
  • Type 2 diabetes is associated with significant renal complications, including albuminuria.

Purpose of the Study:

  • To investigate the renal protective effects of chronic chymase inhibition in a mouse model of type 2 diabetes.

Main Methods:

  • Diabetic (db/db) and control (db/m) mice received chronic chymase inhibitor or vehicle infusion for 8 weeks.
  • Urinary albumin excretion (UalbV) and urinary neutrophil gelatinase-associated lipocalin (UNGAL V) were measured.
  • Renal histopathology, specifically mesangial matrix expansion, was assessed.

Main Results:

  • Chymase inhibition significantly reduced the increase in UalbV in diabetic mice compared to vehicle-treated controls.
  • UNGAL V increased significantly only in vehicle-treated diabetic mice.
  • Reduced mesangial matrix expansion was observed in the glomeruli of diabetic mice treated with chymase inhibitor.

Conclusions:

  • Chronic chymase inhibition demonstrated a renal protective effect in type 2 diabetes.
  • Renal chymase plays a role in the progression of albuminuria in type 2 diabetes kidney disease.
Keywords:
angiotensin IIdb/db mousefibrosis

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