Structure and biological function
α-KLOTHO is a protein belonging to the glycosyl hydrolase 1 family. It can be found either as a membrane bound or a secreted form, which is the more abundant form. α-KLOTHO is expressed in kidney, small intestine, placenta and prostate. The soluble peptide can be found in serum and cerebrospinal fluid. KLOTHO is a co-receptor of fibroblast growth factor 23 (FGF-23) and it plays an important role in the calcium/ phosphorus homeostasis regulation by e.g. inhibiting active vitamin D synthesis. Further, it is also known as an anti-aging-hormone by extending life span by inhibiting insulin/ IGF1 signaling pathway, as experiments in mice showed. Although there are some assay systems for measuring α-KLOTHO available, current existing clinical data is noncoherent. Therefore, we decided to use our FluoBolt™-Technology to provide a high sensitivity α-KLOTHO assay for clinical research, that may improve data consistency. Determination of serum α-KLOTHO has been used for studying the following topics:
Involvement in diseases :
CKD is probably the most intensively studied area using KLOTHO as biomarker, which is not surprising considering the link to phosphorus homeostasis and vitamin D via its interaction with FGF-23. Clinical data are partly contradictory but most meta analyses (e.g. Liu et al., 2019) showed a positive correlation with eGFR and that KLOTHO serum levels are associated with an increased risk of reaching adverse kidney outcomes in patients with CKD. Overall KLOTHO could be used as a novel indicator for early diagnosis and prognostic assessment of CKD, but prospective studies with larger sample sizes are still required.
It has been found, that KLOTHO functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). It seems, that this protein is a favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. However, this finding is based on expression studies in cell culture models and the role of serum KLOTHO levels remains to be established.
There are a lot of evidences that KLOTHO deficiency correlates with the occurrence and development of coronary artery disease, atherosclerosis, myocardial infarction and left ventricular hypertrophy. This may be a result of the inhibition of insulin/insulin-like growth factor-1 signaling pathway by KLOTHO thus regulating oxidative stress and reducing cell death. These antioxidative and antiapoptotic actions could be considered as a novel protective factor in cardiovascular disease and heart injury. Soluble KLOTHO has been associated with mortality and cardiovascular events, e.g. in hemodialysis patients.
KLOTHO deficiency has been linked to aging-like phenotypes such as osteoporosis, cognitive impairment and sarcopenia. Although serum KLOTHO protein levels have been associated with the degree of bone mineral density (BMD) in e.g. hemodialysis patients, no association with fracture risk was found. More prospective studies with larger sample sizes are required to clarify the role of this protein in bone disorders