Atypical Protein Kinase C Zeta Mediates Renal NF-kB Signaling During Crystal-Induced Kidney Injury

Kidney stones, affecting 1 in 10 people, form due to the buildup of crystals in renal tubules. Formerly, the Weimbs Lab demonstrated that tubular dilation aids in crystal clearance, but the mechanism remains unclear. Atypical Protein Kinase C Zeta (aPKCζ) has emerged as a key regulator of renal crystal clearance. This study investigates the relationship between aPKCζ and the Nuclear Factor Kappa B (NF-κB) signaling pathway, a key mediator of renal immune responses. We compared wildtype (WT) and aPKCζ-knockout (aPKCζ-/-) mice on a sodium oxalate diet promoting crystal buildup. At baseline, aPKCζ deficiency showed a significant reduction in NF-κB abundance in renal epithelial cells. Following injury, WT kidneys showed increasing NF-κB activation, while aPKCζ-/- kidneys exhibited only a modest increase. These findings reveal that aPKCζ is critical for proper NF-κB activation in crystal-induced renal injury and may serve as a therapeutic target to mitigate inflammation in kidney diseases.