TNF and Nephropathy: Klotho has been seen in excess to inhibit the NF-kB pathway, leading to the decreased production of TNF-α, interleukin 6 (IL-6), and IL-12, and to attenuate the cyclosporine A-induced nephropathy in vivo and in vitro [32]. In addition, one more vital role of Klotho is to suppress NADPH oxidase 2 (Nox2) protein expression in rat aortic smooth muscle cells and decrease oxidative stress, and it can also affect retinoic acid-inducible gene I (RIG-I) mediated inflammation [33-34].