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Fibroblast COX-2 Expression in the Development of Progressive Kidney Fibrosis
Ming-Tsun Tsai1,2,3, Mengdi Jiang1,2, Yu Pan1,2
1Division of Nephrology and Hypertension, Department of Medicine.
Journal of the American Society of Nephrology : JASN
|August 6, 2026
Summary
Fibroblast cyclooxygenase-2 (COX-2) plays a protective role in kidney fibrosis by modulating macrophage phenotype. Deleting COX-2 in fibroblasts exacerbates kidney fibrosis and promotes pro-inflammatory macrophages.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Kidney fibrosis involves fibroblast and macrophage contributions to extracellular matrix deposition.
- The interaction between fibroblasts and macrophages in kidney fibrosis is not fully understood.
- Kidney prostaglandins may limit fibroblast activity and myofibroblast transformation.
Purpose of the Study:
- To investigate the role of fibroblast cyclooxygenase-2 (COX-2) in kidney fibrosis.
- To explore the interaction between fibroblasts and macrophages in the fibrotic kidney microenvironment.
Main Methods:
- Utilized inducible PDGFRß-Cre mice crossed with floxed mice to selectively delete COX-2 in fibroblasts.
- Employed unilateral ureteral obstruction as a model for progressive kidney fibrosis.
- Administered clodronate to deplete kidney macrophages.
Main Results:
- Selective deletion of fibroblast COX-2 (FibCOX-2-/-) significantly increased kidney fibrosis.
- FibCOX-2-/- mice exhibited kidney macrophages with a proinflammatory and profibrotic phenotype, notably expressing higher levels of SPP1/osteopontin.
- Depletion of kidney macrophages ameliorated fibrosis in FibCOX-2-/- mice.
Conclusions:
- Fibroblast COX-2 expression is protective against progressive kidney fibrosis.
- Fibroblast COX-2 may regulate macrophage phenotype, influencing the fibrotic process.
- Targeting fibroblast COX-2 or macrophage interactions could offer therapeutic strategies for chronic kidney injury.
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