Although the role of the erythropoietin (EPO) receptor (EpoR) in erythropoiesis has been known for decades, its role in nonhematopoietic tissues is still not well defined. Klotho has been shown and EPo has been suggested to protect against acute ischemia-reperfusion injury in the kidney. Here we found in rat kidney and in a rat renal tubular epithelial cell line (NRK cells) EpoR transcript and ...

BACKGROUND α-Klotho is a protein mainly produced in the kidney. Its circulating form has been suggested to link renal damage and distant tissue pathology. As three assays to measure α-Klotho became commercially available, we performed an evaluation of these commercially available Klotho assays. METHODS We studied within-run variation, between-run variation, matrix effects, linearity, and reco...

The concept of fractal geometry is useful for the analysis of irregular and complex structures often seen in nature. Here we apply this concept to investigate the structural mechanism of the development of pulmonary emphysema in the klotho mouse, which, after milk feeding, exhibits characteristics resembling aging and develops emphysema. We calculated the relationships between perimeter and siz...

The longevity gene klotho has numerous physiological functions, such as regulating calcium and phosphorus levels, delaying senescence, improving cognition, reducing oxidative stress, and protecting vascular endothelial cells. This study tested whether 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a small molecule with antiaging effects, regulates the expression and physiological effec...

Cardiomyocyte apoptosis is a common pathological alteration in heart disease which results in systolic dysfunction or sudden death. Klotho is a novel anti-aging hormone. We tested the effects of klotho on cell apoptosis in isoproterenol-treated cardiomyocytes. In BALB/c mice, cardiac injury was induced by subcutaneous injection of isoproterenol (5 mg/kg, for 9 days, s.c.). Klotho (0.01 mg/kg, e...

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the US and is associated with an abnormal inflammatory response to cigarette smoke (CS). Exposure to CS induces oxidative stress and can result in cellular senescence in the lung. Cellular senescence can then lead to decreased proliferation of epithelial cells, the destruction of alveolar structure and...

BACKGROUND Klotho and fibroblast growth factor 23 (FGF23) are key regulators of mineral metabolism in renal insufficiency. FGF23 levels have been shown to increase early in chronic kidney disease (CKD); however, the corresponding soluble Klotho levels at the different CKD stages are not known. METHODS Soluble Klotho, FGF23, parathyroid hormone (PTH), 1,25-dihydroxy vitamin D(3) (1,25D) and ot...

The klotho gene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ...

The reversal of soft-tissue abnormalities and prolonged lifespan observed in klotho(-/-) mice following genetic inactivation of 1alpha-hydroxylase underscores the pathophysiological role of 1,25-dihydroxyvitamin D in mediating some of the premature aging-like features observed in klotho(-/-) mice.

It has been recently established that Klotho coreceptors associate with fibroblast growth factor (FGF) receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here, we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FG...