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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
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Pleiotropic Actions of FGF23.

Reinhold G Erben1

  • 11 Department of Biomedical Sciences, Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.

Toxicologic Pathology
|November 4, 2017
PubMed
Summary

Fibroblast growth factor-23 (FGF23) is a pleiotropic hormone linking bone to other organs. It regulates phosphate, vitamin D, calcium, and sodium, impacting kidney disease and mineralization.

Area of Science:

  • Endocrinology
  • Bone Biology
  • Nephrology

Background:

  • Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating phosphate and vitamin D metabolism.
  • FGF23 exerts endocrine effects via FGF receptor 1 (FGFR1) and α-Klotho (Klotho) co-receptor.
  • Dysregulation of FGF23 is implicated in chronic kidney disease pathophysiology.

Purpose of the Study:

  • To elucidate the multifaceted roles of FGF23 beyond phosphate homeostasis.
  • To explore FGF23's impact on renal tubular function and mineral metabolism.
  • To investigate FGF23's auto-/paracrine and potential cardiac signaling pathways.

Main Methods:

  • Review of FGF23 signaling pathways and their physiological consequences.
  • Analysis of FGF23's effects on renal sodium-phosphate cotransporters (Npt2a, Npt2c) and 1α-hydroxylase.
Keywords:
bonebone mineralizationcardiovascular systemendocrine systemmineral metabolismrenaltransgenic animals

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  • Examination of Klotho-dependent and independent FGF23 actions.

    • Main Results:

    • FGF23 suppresses renal phosphate reabsorption and vitamin D production.
    • FGF23 promotes renal calcium and sodium reabsorption via Klotho-dependent pathways.
    • FGF23 acts as an auto-/paracrine suppressor of mineralization and may target the heart.

    Conclusions:

    • FGF23 is a pleiotropic hormone with significant endocrine, auto-/paracrine, and potentially paracrine functions.
    • FGF23 links bone metabolism with kidney, cardiovascular, and mineral homeostasis.
    • Understanding FGF23's diverse roles is crucial for managing metabolic bone diseases and chronic kidney disease.