Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

Ying Sun, Weici Zhang, Jilly F. Evans, Annarosa Floreani, Zhengsheng Zou, Yukiko Nishio, Ruizhao Qi, Patrick S Leung, Christopher Bowlus, M. Eric Gershwin

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

Autotaxin (ATX) is a 125-kD type II ectonucleotide pyrophosphatase/phosphodiesterase (ENPP2 or NPP2) originally discovered as an unknown “autocrine motility factor” in human melanoma cells. In addition to its pyrophosphatase/phosphodiesterase activities ATX has lysophospholipase D (lysoPLD) activity, catalyzing the conversion of lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). ATX is the only ENPP family member with lysoPLD activity and it produces most of the LPA in circulation. In support of this, ATX heterozygous mice have 50% of normal LPA plasma levels. The ATX-LPA signaling axis plays an important role in both normal physiology and disease pathogenesis and recently has been linked to pruritus in chronic cholestatic liver diseases, including primary biliary cholangitis (PBC). Several lines of evidence have suggested that a circulating puritogen is responsible, but the identification of the molecule has yet to be definitively identified. In contrast, plasma ATX activity is strongly associated with pruritus in PBC, suggesting a targetable molecule for treatment. We review herein the biochemistry of ATX and the rationale for its role in pruritus.

Original languageEnglish (US)
Pages (from-to)795-800
Number of pages6
JournalAutoimmunity Reviews
Volume15
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • autoimmunity
  • Autotaxin
  • cholestatic liver diseases
  • lysophosphatidylcholine
  • pruritus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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