Proinflammatory cytokines contribute to renal injury, but the downstream effectors within
kidney cells are not well understood. One candidate effector is Klotho, a protein expressed
by renal cells that has antiaging properties; Klotho-deficient mice have an accelerated aging-
like phenotype, including vascular injury and renal injury. Whether proinflammatory
cytokines, such as TNF and TNF-like weak inducer of apoptosis (TWEAK), modulate Klotho
is unknown. In mice, exogenous administration of TWEAK decreased expression of Klotho in …