Cell-Specific Roles of Angiopoietin-2 in CKD
Abstract
Key points: Global deletion of angiopoietin-2 protected against the progression of CKD. Endothelial cell-derived angiopoietin-2 drove early inflammation by promoting endothelial activation. Tubular epithelial cell-derived angiopoietin-2 contributed to functional decline and kidney fibrosis in advanced CKD.
Background: CKD is driven by inflammation, vascular dysfunction, and fibrosis, with emerging evidence implicating angiopoietin-2 as a key mediator. While angiopoietin-2 is produced by endothelial cells and upregulated in injured tubular epithelial cells (TECs), the distinct contributions of endothelial cell-derived and TEC-derived angiopoietin-2 remain unclear. This study defines the cell type-specific roles of angiopoietin-2 in CKD pathogenesis.
Methods: We examined kidney transcriptomes and outcomes from the Taipei Renal Transcriptomics and Outcomes Investigation cohort, with fibrosis assessed by histology and RNA sequencing. Global, endothelial cell-specific, and TEC-specific angiopoietin-2 knockout mice were subjected to experimental CKD. Kidney injury, inflammation, vascular changes, and fibrosis were evaluated using histologic, molecular, and imaging analyses.
Results: In patients with CKD, elevated kidney ANGPT2 mRNA was associated with lower estimated glomerular filtration rate, greater kidney fibrosis, and adverse kidney outcomes. Global deletion of angiopoietin-2 in mice preserved kidney function and reduced inflammation, vascular rarefaction, and fibrosis during…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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