Cellular signaling in pseudoxanthoma elasticum: an update.

Abstract:

:Pseudoxanthoma elasticum is an autosomal recessive genodermatosis with variable expression, due to mutations in the ABCC6 or ENPP1 gene. It is characterized by elastic fiber mineralization and fragmentation, resulting in skin, eye and cardiovascular symptoms. Significant advances have been made in the last 20 years with respect to the phenotypic characterization and pathophysiological mechanisms leading to elastic fiber mineralization. Nonetheless, the substrates of the ABCC6 transporter - the main cause of PXE - remain currently unknown. Though the precise mechanisms linking the ABCC6 transporter to mineralization of the extracellular matrix are unclear, several studies have looked into the cellular consequences of ABCC6 deficiency in PXE patients and/or animal models. In this paper, we compile the evidence on cellular signaling in PXE, which seems to revolve mainly around TGF-βs, BMPs and inorganic pyrophosphate signaling cascades. Where conflicting results or fragmented data are present, we address these with novel signaling data. This way, we aim to better understand the up- and down-stream signaling of TGF-βs and BMPs in PXE and we demonstrate that ANKH deficiency can be an additional mechanism contributing to decreased serum PPi levels in PXE patients.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Van Gils M,Nollet L,Verly E,Deianova N,Vanakker OM

doi

10.1016/j.cellsig.2018.12.009

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

119-129

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(18)30319-X

journal_volume

55

pub_type

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