Fibroblast growth factor-23 (FGF23) is a hormone mainly produced in osteoblasts and osteocytes, at least under physiological conditions. FGF23 was discovered as a plasma phosphate-lowering hormone, suppressing phosphate reabsorption and vitamin D hormone production in proximal tubular epithelium in the kidney. However, more recently, it was reported that FGF23 may also act as a prohypertrophic factor in the heart, as a paracrine regulator of bone mineralization, as inhibitor of leukocyte recruitment, and as a regulator of calcium and sodium reabsorption in distal renal tubules. Therefore, FGF23 has emerged as a pleiotropic factor with multiple endocrine and auto/paracrine effects in different organ systems. These novel, and in many cases, unexpected discoveries have profoundly changed the field, and have provided completely new perspectives on the putative role of increased FGF23 secretion in maladaptive processes occurring in a number of etiologically completely different diseases such as chronic kidney disease, myocardial infarction, hypertension, and disorders characterized by impaired bone mineralization. However, the pathophysiological importance of these newly discovered functions of FGF23 still needs to be more clearly defined.
The transmembrane protein Klotho shares homology with glycosidases, and was originally described as an anti-aging factor. There is now ample evidence that transmembrane Klotho functions as an obligatory co-receptor for FGF23 signaling. However, Klotho circulates in the blood stream also as a soluble form lacking the transmembrane domain. Whether soluble Klotho has FGF23 independent effects as a hormone or as a glycosidase remains to be a controversial issue.
The purpose of this Research Topic is to address some of the unresolved questions in this rapidly expanding field, drawing a comprehensive picture of the current state of the art. Current key questions are: How is FGF23 secretion controlled? What is the relative contribution of the four different FGF receptors in FGF23 signaling in different organ systems? What is the interrelationship between FGF23 and the immune system? What is the mechanistic basis for the strong association between circulating FGF23 and heart hypertrophy as well as disease progression in patients with chronic kidney disease? Is there a role of FGF23 in cardiovascular diseases in general? What is the pathophysiological relevance of FGF23 as auto-/paracrine inhibitor of bone mineralization? How can circulating concentrations of soluble Klotho be measured in a reliable fashion? What is the mechanism of action of soluble Klotho, and what is its role in health and disease?
This Research Topic is dedicated to shed more light on these questions and to foster the advancement of the field by combining molecular, animal experimental, and clinical points of view.
Fibroblast growth factor-23 (FGF23) is a hormone mainly produced in osteoblasts and osteocytes, at least under physiological conditions. FGF23 was discovered as a plasma phosphate-lowering hormone, suppressing phosphate reabsorption and vitamin D hormone production in proximal tubular epithelium in the kidney. However, more recently, it was reported that FGF23 may also act as a prohypertrophic factor in the heart, as a paracrine regulator of bone mineralization, as inhibitor of leukocyte recruitment, and as a regulator of calcium and sodium reabsorption in distal renal tubules. Therefore, FGF23 has emerged as a pleiotropic factor with multiple endocrine and auto/paracrine effects in different organ systems. These novel, and in many cases, unexpected discoveries have profoundly changed the field, and have provided completely new perspectives on the putative role of increased FGF23 secretion in maladaptive processes occurring in a number of etiologically completely different diseases such as chronic kidney disease, myocardial infarction, hypertension, and disorders characterized by impaired bone mineralization. However, the pathophysiological importance of these newly discovered functions of FGF23 still needs to be more clearly defined.
The transmembrane protein Klotho shares homology with glycosidases, and was originally described as an anti-aging factor. There is now ample evidence that transmembrane Klotho functions as an obligatory co-receptor for FGF23 signaling. However, Klotho circulates in the blood stream also as a soluble form lacking the transmembrane domain. Whether soluble Klotho has FGF23 independent effects as a hormone or as a glycosidase remains to be a controversial issue.
The purpose of this Research Topic is to address some of the unresolved questions in this rapidly expanding field, drawing a comprehensive picture of the current state of the art. Current key questions are: How is FGF23 secretion controlled? What is the relative contribution of the four different FGF receptors in FGF23 signaling in different organ systems? What is the interrelationship between FGF23 and the immune system? What is the mechanistic basis for the strong association between circulating FGF23 and heart hypertrophy as well as disease progression in patients with chronic kidney disease? Is there a role of FGF23 in cardiovascular diseases in general? What is the pathophysiological relevance of FGF23 as auto-/paracrine inhibitor of bone mineralization? How can circulating concentrations of soluble Klotho be measured in a reliable fashion? What is the mechanism of action of soluble Klotho, and what is its role in health and disease?
This Research Topic is dedicated to shed more light on these questions and to foster the advancement of the field by combining molecular, animal experimental, and clinical points of view.
