Endocrine FGFs and Klothos, 2012
Advances in Experimental Medicine and Biology Series, Vol. 728

Coordinator: Kuro-o Makoto

Language: English

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210 p. · 17.8x25.4 cm · Paperback
Fibroblast growth factors (FGFs) have been recognized primarily as autocrine/paracrine factors that regulate embryonic development and organogenesis. However, recent studies have revealed that some FGFs function as endocrine factors and regulate various metabolic processes in adulthood. Such FGFs, collectively called endocrine FGFs, are comprised of three members (FGF15/19, FGF21, and FGF23: FGF15 is the mouse ortholog of human FGF19). These endocrine FGFs share a common structural feature that enables the endocrine mode of action at the expense of the affinity to FGF receptors. To restore the affinity to FGF receptors in their target organs, the endocrine FGFs have designated the Klotho family of transmembrane proteins as obligate co-receptors. By expressing Klothos in a tissue-specific manner, this unique co-receptor system also enables the endocrine FGFs to specify their target organs among many tissues that express FGF receptors.

The Structural Biology of the FGF19 Subfamily.- Klotho and bKlotho.- FGF23 and Syndromes of Abnormal Renal Phosphate Handling.- Evidence For FGF23 Involvement in a Bone‑Kidney Axis Regulating Bone Mineralization and Systemic Phosphate and Vitamin D Homeostasis.- FGF23, Klotho and Vitamin D Interactions: What Have We Learned from In Vivo Mouse Genetics Studies?.- FGF23 and the Parathyroid.- Regulation of Ion Channels by Secreted Klotho.- FGF23 in Chronic Kidney Disease.- Secreted Klotho and Chronic Kidney Disease.- FGF23 as a Novel Therapeutic Target.- Physiology of FGF15/19.- FGF19 and Cancer.- Understanding the Structure‑Function Relationship Between FGF19 and its Mitogenic and Metabolic Activities.- FGF21 as a Therapeutic Reagent.

MAKOTO KURO-O is an Associate Professor in the Pathology Department at the University of Texas Southwestern Medical Center at Dallas (UT Southwestern). He also has an appointment to the Pak Center for Mineral Metabolism and the Simmons Comprehensive Cancer Center in UT Southwestern. He received his MD and PhD from the University of Tokyo, Japan. His major research interests include molecular mechanisms of aging and age-related diseases with special reference to chronic kidney disease. He is a member of the American Society of Nephrology (ASN).

Discusses potential of FGF23 and Klotho as novel diagnostic markers and therapeutic targets for chronic kidney disease Gives an overview of current knowledge on FGF19 and FGF21 Comprehensive in scope