Molecular targeting of renal inflammation using drug delivery technology to inhibit NF-κB improves renal recovery in chronic kidney disease.

American Journal of Physiology. Renal Physiology
Alejandro R ChadeGene L Bidwell

Abstract

Inflammation is a major determinant for the progression of chronic kidney disease (CKD). NF-κB is a master transcription factor upregulated in CKD that promotes inflammation and regulates apoptosis and vascular remodeling. We aimed to modulate this pathway for CKD therapy in a swine model of CKD using a peptide inhibitor of the NF-κB p50 subunit (p50i) fused to a protein carrier [elastin-like polypeptide (ELP)] and equipped with a cell-penetrating peptide (SynB1). We hypothesized that intrarenal SynB1-ELP-p50i therapy would inhibit NF-κB-driven inflammation and induce renal recovery. CKD was induced in 14 pigs. After 6 wk, pigs received single intrarenal SynB1-ELP-p50i therapy (10 mg/kg) or placebo (n = 7 each). Renal hemodynamics were quantified in vivo using multidetector computed tomography before and 8 wk after treatment. Pigs were then euthanized. Ex vivo experiments were performed to quantify renal activation of NF-κB, expression of downstream mediators of NF-κB signaling, renal microvascular density, inflammation, and fibrosis. Fourteen weeks of CKD stimulated NF-κB signaling and downstream mediators (e.g., TNF-α, monocyte chemoattractant protein-1, and IL-6) accompanying loss of renal function, inflammation, fibrosis, a...Continue Reading

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Citations

Aug 8, 2021·International Journal of Molecular Sciences·Md Jamal UddinHunjoo Ha
Aug 17, 2021·American Journal of Physiology. Renal Physiology·Alejandro R ChadeGene L Bidwell

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Methods Mentioned

BETA
nuclear translocation
ELISA
PCR
confocal microscopy

Software Mentioned

ANALYZE
ImageJ
Nikon Elements

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