αKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.
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http://dx.doi.org/10.2215/CJN.02840320 | DOI Listing |
J Cachexia Sarcopenia Muscle
February 2025
Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA.
Background: A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute of Immunology, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.
Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor gene and Klotho protein in the immunopathogenesis of gliomas. We examined genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method.
View Article and Find Full Text PDFInt J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
View Article and Find Full Text PDFFEBS Lett
January 2025
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Soluble, circulating Klotho (sKlotho) is essential for normal health and renal function. sKlotho is shed from the renal distal convoluted tubule (DCT), its primary source, via enzymatic cleavage. However, the physiologic mechanisms that control sKlotho production, trafficking, and shedding are not fully defined.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
Background: Current evidence regarding the effects of serum Klotho among patients with metabolic syndrome (MetS) is scarce. This study explored the relationship between serum Klotho levels and the odds of chronic kidney disease (CKD) in middle-aged and older populations with MetS.
Materials And Methods: This cross-sectional study analyzed data from 4870 adults aged 40-79 years who participated in the National Health and Nutrition Survey (NHANES) from 2007 to 2016.
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