Related Experiment Video
Updated: Jan 29, 2026
04:37
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
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TNFα and Endothelial IL-1 Receptor Signaling Drive Peritubular Capillary Regression and Fibrosis in Obstructive
Charmain F Johnson1, Kate Wheeler1, Jun Xie1
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Biorxiv : the Preprint Server for Biology
|January 28, 2026
Summary
Tumor necrosis factor-alpha (TNFα) and interleukin-1 receptor 1 (IL-1R1) signaling cooperatively drive pathological capillary loss in chronic kidney disease. Dual targeting may preserve peritubular capillaries, reducing kidney injury and fibrosis.
Area of Science:
- Nephrology
- Immunology
- Vascular Biology
Background:
- Capillary regression destabilizes tissue homeostasis and causes chronic organ dysfunction.
- Inflammatory pathways driving pathological vessel loss are not fully understood.
- Tumor necrosis factor-alpha (TNFα) and IL-1 were previously implicated in physiological vessel regression.
Purpose of the Study:
- To investigate the role of TNFα and endothelial IL-1 receptor 1 (IL-1R1) in pathological capillary regression in adult mice.
- To determine if combined TNFα and IL-1R1 signaling drives capillary loss in a murine model of chronic kidney injury.
Main Methods:
- Utilized a murine model of irreversible unilateral ureteral obstruction (UUO) to induce kidney injury.
- Examined mice genetically deficient in TNFα, IL-1R1, or both (double knockout, DKO).
- Assessed peritubular capillary (PTC) regression, tubular epithelial injury (KIM-1), and fibrosis at 10 days post-UUO.
Main Results:
- Loss of individual TNFα or IL-1R1 genes did not significantly affect PTC regression.
- DKO mice exhibited significantly reduced PTC regression compared to controls.
- Preservation of PTCs in DKO mice correlated with decreased KIM-1 expression and reduced renal fibrosis.
Conclusions:
- TNFα and endothelial IL-1R1 cooperatively drive pathological capillary regression in the UUO model of chronic kidney injury.
- Combined inhibition of TNFα and IL-1R1 signaling may preserve PTC integrity.
- Preserving PTCs correlates with reduced renal tubular injury and fibrosis in chronic kidney disease.
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