Molecular Targeting of Renal Inflammation using Drug Delivery Technology to Inhibit NF-kB Improves Renal Recovery in Chronic Kidney Disease.

Molecular Targeting of Renal Inflammation using Drug Delivery Technology to Inhibit NF-kB Improves Renal Recovery in Chronic Kidney Disease. Am J Physiol Renal Physiol. 2020 Jun 15;: Authors: Chade AR, Williams ML, Engel JE, Williams E, Bidwell GL Abstract Inflammation is a major determinant for the progression of chronic kidney disease (CKD). Nuclear-factor-kappa-B (NF-kB) is a master transcription factor up-regulated in CKD that promotes inflammation, 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-kB p50 subunit (p50i) fused to a protein carrier (elastin-like polypeptide, ELP) and equipped with a cell-penetrating peptide (SynB1). We hypothesize that intra-renal SynB1-ELP-p50i therapy will inhibit NF-kB-driven inflammation and induce renal recovery. CKD was induced in 14 pigs. After 6 weeks, pigs received single intra-renal SynB1-ELP-p50i therapy (10 mg/kg) or placebo (n=7 each). Renal hemodynamics were quantified in vivo using multi-detector CT before and 8 weeks after treatment. Pigs were then euthanized. Ex vivo studies were performed to quantify renal activation of NF-kB, expression of downstream mediators of NF-kB signaling, renal microvascular density, inflammation, and fibrosis. Fourteen weeks of CKD stimulated NF-kB signaling and downstream mediators (e.g. TNF-α, MCP-1, and-6) accompanying loss of renal function, inf...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research