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NF-κB-driven lymphangiogenesis affects kidney function via a VEGFR-3-mediated pathway
Arin L Melkonian1,2, Amie M Traylor1, Anna A Zmijewska1
1Division of Nephrology, Department of Medicine.
JCI Insight
|January 23, 2026
Summary
RelA in lymphatic vessels is crucial for kidney repair after injury. Its absence worsens kidney function and impairs lymphangiogenesis, highlighting RelA as a therapeutic target for acute kidney injury.
Area of Science:
- Renal physiology and immunology
- Lymphatic biology
- Inflammation and injury response
Background:
- The lymphatic system's role in non-lymphoid organs like the kidney is under-investigated.
- Previous studies linked NF-κB signaling (p50 subunit) to lymphatic vessel density.
- The specific role of RelA in kidney lymphangiogenesis post-injury was unknown.
Purpose of the Study:
- To investigate the role of RelA in lymphatic vessel growth and kidney function following acute kidney injury (AKI).
- To determine if RelA in VEGFR-3+ cells is essential for lymphangiogenesis after AKI.
Main Methods:
- Utilized an inducible, lymphatic-specific RelA knockout mouse model.
- Assessed kidney function, histology, and lymphatic vessel markers (VEGFR-3, LYVE-1, PROX-1, podoplanin) post-AKI.
- Analyzed immune cell trafficking patterns.
Main Results:
- RelA knockout mice showed significantly impaired kidney function and altered histology after AKI.
- VEGFR-3-dependent lymphangiogenesis was significantly reduced in knockout mice.
- Immune cell trafficking was dysregulated, with compensatory upregulation of PROX-1 and podoplanin despite decreased VEGFR-3 and LYVE-1.
Conclusions:
- RelA is essential for protective lymphangiogenesis in the kidney following acute kidney injury.
- RelA acts as a critical regulator of inflammation and lymphatic repair post-kidney injury.
- Targeting RelA may offer a therapeutic strategy for improving outcomes in acute kidney injury.
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