Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

• Published in: Toxins Vol. 12; no. 3; p. 185
• Main Authors: Muñoz-Castañeda, Juan Rafael, Rodelo-Haad, Cristian, Pendon-Ruiz de Mier, Maria Victoria, Martin-Malo, Alejandro, Santamaria, Rafael, Rodriguez, Mariano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16-03-2020; MDPI
• Subjects: Binding sites; Blood vessels; Bone and Bones - metabolism; cardiorenal syndrome; Cardiovascular disease; Cardiovascular diseases; Cellular signal transduction; Chronic kidney failure; ckd; Complications and side effects; Diabetes; fgfg23; Fibroblast Growth Factor-23; Fibroblast growth factors; Fibroblast Growth Factors - metabolism; Fibroblasts; Glucuronidase - metabolism; Growth factors; Health aspects; Heart; Humans; Kidney - metabolism; Kidney diseases; Kidneys; Kinases; klotho; Klotho protein; Klotho Proteins; Ligands; Medical research; Metabolism; Mineral metabolism; Myocardium - metabolism; Organs; Phosphaturia; Physiological aspects; Proteins; Renal failure; Renal function; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - metabolism; Renal tubules; Review; Risk factors; Signaling; Therapeutic applications; Transcription factors; Wnt protein; Wnt proteins; Wnt Signaling Pathway; wnt/β-catenin; β-Catenin; Spain; Klotho; CKD; Wnt/β-catenin; FGFG23; cardiorenal syndrome
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins12030185

Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules. However, Klotho expression is reduced as soon as renal function is starting to fail to generate a state of FGF23 resistance. Changes in these proteins directly affect to other mineral metabolism parameters; they may affect renal function and can produce damage in other organs such as bone, heart, or vessels. Some of the mechanisms responsible for the changes in FGF23 and Klotho levels are related to modifications in the Wnt signaling. This review examines the link between FGF23/Klotho and Wnt/β-catenin in different organs: kidney, heart, and bone. Activation of the canonical Wnt signaling produces changes in FGF23 and Klotho and vice versa; therefore, this pathway emerges as a potential therapeutic target that may help to prevent CKD-associated complications.