Klotho as a Therapeutic Target during the Development of Renal Fibrosis

Systemic symptoms such as the ectopic calcification, atrophy of skin and muscle, and impaired sexual function observed in chronic kidney diseases (CKD) have been reported to coincide with those observed in geriatric symptoms. Regarding the kidney, clinical/pathological characteristics in CKD patients also coincide with those in the aging kidney. These findings suggest common mechanisms in the development of both CKD and aging. Our investigation of aging factors associated with renal fibrosis in IgA nephropathy patients revealed a significant correlation between accumulation of cells with an arrested cell cycle and decreased expression of Klotho protein. Because cell cycle arrest has a protective effect on organs in the acute phase, the proposed therapeutic target against the aging process is to maintain expression of Klotho protein. In addition, it is recognized that TGF-β1 plays a central role in the development of renal fibrosis. However, TGF-β1 has also been reported to decrease expression of Klotho protein. In this report, we provide an interpretation of our new treatment strategy which involves controlling histone methylation.