Related Experiment Video

Updated: Oct 4, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

341

Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor

Yi Guan1, Linda Davis2, Matthew D Breyer3

  • 1Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.

Prostaglandins & Other Lipid Mediators
|February 8, 2022
PubMed

Insights

Diabetic nephropathy involves cyclooxygenase-2 (COX2). Targeting the EP4 receptor, not COX2, reduced kidney damage and albuminuria in diabetic mice, offering a safer therapeutic approach.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic nephropathy (DN) is a severe complication of diabetes, contributing to mortality.
  • Cyclooxygenase (COX) and its products are implicated in DN pathogenesis.
  • Increased COX2 expression is observed in diabetic kidneys.

Purpose of the Study:

  • To investigate the role of COX2-derived prostanoids in DN.
  • To test if EP4 receptor activation mediates DN-induced endothelial dysfunction.
  • To evaluate EP4 receptor antagonism as a therapeutic strategy for DN.

Main Methods:

  • Studied STZ-induced DBA and Akita/DBA mice models of diabetes.
  • Administered COX2 inhibitors and EP4 antagonists.
  • Assessed albuminuria, histological lesions, and renal angiopoietin-1/tie-2 system expression.

Main Results:

  • COX2 inhibition reduced albuminuria and kidney damage, upregulating angiopoietin-1/tie-2.
  • Prostaglandin E2 (PGE2) and its receptor EP4 are present in glomeruli.
  • EP4 receptor blockade significantly decreased albuminuria in diabetic mice.

Conclusions:

  • Diabetes-associated COX2 overexpression drives renal PGE2 production and endothelial dysfunction via glomerular EP4.
  • EP4 receptor antagonism shows promise for treating diabetic nephropathy.
  • Targeting EP4 offers a potentially safer alternative to COX2 inhibitors for DN treatment.
Keywords:
Cyclooxygenase-2Diabetic nephropathyEP4 receptor

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