αKlotho protein has therapeutic activity in contrast-induced acute kidney injury by limiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy

Contrast-induced acute kidney injury (CI-AKI) is a main cause of hospital-acquired renal failure. Nevertheless, limited measures have been shown to be effective for the treatment of CI-AKI. Here, we demonstrated that alpha Klotho, which is highly expressed in kidney, has therapeutic activity in CI-AKI. Our data showed that alpha Klotho expression levels were decreased both in the kidney and serum of CI-AKI mice. Administration of alpha Klotho protein protected the kidney and HK-2 cells against contrast-induced injury. Mechanistically, alpha Klotho reduced contrast-induced renal tubular cells pyroptosis by limiting NLRP3 inflammasome activation. Meanwhile, alpha Klotho upregulated autophagy via inhibiting the AKT/mTOR pathway and decreased mitochondrial ROS level. Inhibition of autophagy blunted the suppression effect of alpha Klotho on NLRP3 inflammasome activation and cell pyroptosis in contrast-treated HK-2 cells. Taken together, our data suggest that alpha Klotho protein protects against CI-AKI through inhibiting NLRP3 inflammasome-mediated pyroptosis, which is likely by promoting autophagy. alpha Klotho may be a promising therapeutic strategy for CI-AKI.