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Cellular signaling in pseudoxanthoma elasticum: an update.

M Van Gils1, L Nollet2, E Verly2

  • 1Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Belgium.

Cellular Signalling
|January 8, 2019
PubMed
Summary

Pseudoxanthoma elasticum (PXE) involves elastic fiber calcification. This study explores cellular signaling pathways, particularly TGF-β and BMP, and identifies ANKH deficiency as a potential contributor to low pyrophosphate levels in PXE.

Keywords:
ABCC6Bone morphogenetic proteinsCell signalingInorganic pyrophosphatePseudoxanthoma elasticumTransforming growth factor β

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Area of Science:

  • Genetics and Molecular Biology
  • Dermatology
  • Biochemistry

Background:

  • Pseudoxanthoma elasticum (PXE) is an inherited disorder causing elastic fiber mineralization.
  • Mutations in ABCC6 or ENPP1 genes lead to PXE, affecting skin, eyes, and cardiovascular health.
  • Despite advances, the ABCC6 transporter's substrates and precise role in mineralization remain unknown.

Purpose of the Study:

  • To review and synthesize current knowledge on cellular signaling in PXE.
  • To investigate the roles of TGF-β, BMP, and inorganic pyrophosphate (PPi) signaling in PXE pathogenesis.
  • To present novel signaling data and clarify upstream/downstream pathways.

Main Methods:

  • Literature review and data compilation on PXE cellular signaling.
  • Analysis of signaling pathways including TGF-β, BMP, and PPi.
  • Investigation of novel signaling data and ANKH deficiency.

Main Results:

  • PXE cellular signaling appears centered on TGF-β, BMP, and PPi cascades.
  • Conflicting data were addressed with new signaling insights.
  • ANKH deficiency was identified as a potential mechanism for reduced serum PPi in PXE patients.

Conclusions:

  • Understanding PXE signaling pathways is crucial for therapeutic development.
  • TGF-β and BMP signaling are key areas for further PXE research.
  • ANKH deficiency offers a new perspective on PPi dysregulation in PXE.