| [ Summary ] |
Klotho protein is primarily expressed in the kidneys. Klotho mutant mice exhibit short life spans, ectopic calcification, skin atrophy, muscle atrophy, and sexual dysfunction, which resemble not only human aging but also systemic complications in patients with end-stage renal failure (ESRD). These findings suggest the hypotheses that Klotho expression regulates aging process, and that Klotho deficiency causes systemic complications in ESRD patients. In fact, a number of reports have supported these hypotheses. Furthermore, recent studies have demonstrated that kidney damage worsens in klotho hetero-mutant mice. In contrast, it is improved by overexpression of the klotho gene with the use of klotho transgenic mice or an adenovirus vector, or Klotho protein injection as observed in various experimental animal models of kidney diseases. Therefore, Klotho is considered to function as a renoprotective protein. Meanwhile, Klotho expression is easily decreased by various stimuli, indicating that restored Klotho expression is a novel therapeutic target related to the development of kidney diseases. |