Soluble α-Klotho in Liver Cirrhosis and Alcoholism

Aims and background: Alpha Klotho is a transmembrane protein that serves as co-receptor for FGF23. Ectodomain of membrane bound a Klotho may be shed by membrane bound proteases (activated, among other factors, by tumor necrosis factor (TNF)-alpha) generating the soluble form of the protein (sKl) that functions as a hormone by itself. It modulates calcium influx into cells, blunts IGF-1/Insulin signaling, promotes synthesis of antioxidants, generally slows down tumor progression, delays cell senescence, is neuroprotective and promotes oligodendrocyte maturation and myelin synthesis, and muscle rejuvenation. It may be involved in inflammation and exerts antifi-brogenic effects. Some of these pathways may become altered in alcoholism or liver cirrhosis, but data are scattered and scarce and an update is required. Method: Literature survey. Results and Conclusions: Alcohol consumption in non-alcoholics is inversely related to sKl, but alcoholic cirrhotics showed higher-than-normal sKl values in association with liver function derangement. In hepatoma cells, the intensity of Klotho staining was related to faster tumor progression and a shortened life span. Among severe alcoholic cirrhotics sKl is directly related to serum TNF-alpha levels, and, inversely, to brain atrophy. Given the antioxidant, anti-inflammatory, and antifibrogenic effects of Klotho, perhaps the increase in cirrhosis (and in other inflammatory conditions, such as sepsis or cancer) reflects an attempt to regulate increased inflammation, but clinical and experimental research is urgently needed in this field.