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Cell-Specific Roles of Angiopoietin-2 in CKD.

An-Jie Luo1, Tyng-Shiuan Gau2, Ming-Tsun Tsai3,4

  • 1Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Journal of the American Society of Nephrology : JASN
|April 14, 2026
PubMed
Summary

Angiopoietin-2 (ANGPT2) drives kidney disease progression. Targeting ANGPT2 from tubular epithelial cells, not endothelial cells, significantly reduces chronic kidney disease (CKD) fibrosis and injury.

Keywords:
CKDendotheliumkidney fibrosismacrophagesmetabolism

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Pathogenesis of Kidney Disease

Background:

  • Chronic kidney disease (CKD) involves inflammation, vascular issues, and fibrosis.
  • Angiopoietin-2 (ANGPT2) is implicated in CKD, but its cell-specific origins (endothelial vs. tubular epithelial cells) are unclear.

Purpose of the Study:

  • To define the distinct roles of endothelial cell-derived and tubular epithelial cell (TEC)-derived angiopoietin-2 in CKD pathogenesis.

Main Methods:

  • Analysis of kidney transcriptomes and outcomes in CKD patients.
  • Utilizing global, endothelial cell-specific, and TEC-specific angiopoietin-2 knockout mouse models for experimental CKD.
  • Comprehensive histological, molecular, and imaging analyses of kidney injury, inflammation, vascular changes, and fibrosis.

Main Results:

  • Elevated kidney ANGPT2 mRNA in CKD patients correlated with reduced kidney function, fibrosis, and poor outcomes.
  • Global angiopoietin-2 knockout mice showed improved kidney function and reduced CKD pathology.
  • Endothelial cell-specific deletion attenuated early inflammation but not late-stage fibrosis.
  • TEC-specific deletion preserved kidney function and reduced fibrosis and vascular injury in late-stage CKD.

Conclusions:

  • Angiopoietin-2 from distinct cell sources plays specific roles in CKD.
  • Endothelial angiopoietin-2 primarily impacts early inflammation.
  • Tubular epithelial cell-derived angiopoietin-2 is crucial for progressive kidney injury and fibrosis.