Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

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

doi:10.1016/j.autrev.2016.03.019

Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

Autoimmun Rev. 2016 Aug;15(8):795-800. doi: 10.1016/j.autrev.2016.03.019. Epub 2016 Mar 24.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, California, USA; Center for the Treatment and Research of Non-Infectious Liver Diseases, Beijing 302 Hospital, Beijing, 100039, China. Electronic address: sunying_302@yahoo.com.
² Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: ddzhang@ucdavis.edu.
³ PharmAkea Therapeutics, San Diego, California, USA. Electronic address: jevans@pharmakea.com.
⁴ Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy. Electronic address: annarosa.floreani@unipd.it.
⁵ Center for the Treatment and Research of Non-Infectious Liver Diseases, Beijing 302 Hospital, Beijing, 100039, China. Electronic address: zszou302@163.com.
⁶ Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: yukiko.n.naramed@gmail.com.
⁷ Department of General Surgery, Beijing 302nd Hospital, Beijing, 10039, China. Electronic address: rzhqi@sina.com.
⁸ Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: psleung@ucdavis.edu.
⁹ Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: clbowlus@ucdavis.edu.
¹⁰ Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: megershwin@ucdavis.edu.

PMID: 27019050
DOI: 10.1016/j.autrev.2016.03.019

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.

Keywords: Autotaxin; autoimmunity; cholestatic liver diseases; lysophosphatidylcholine; pruritus.

Publication types

Review

MeSH terms

Animals
Biosynthetic Pathways
Cholangitis / pathology*
Humans
Lysophospholipids / biosynthesis*
Phosphoric Diester Hydrolases / chemistry
Phosphoric Diester Hydrolases / genetics
Phosphoric Diester Hydrolases / metabolism*
Pruritus / metabolism*

Substances

Lysophospholipids
Phosphoric Diester Hydrolases
alkylglycerophosphoethanolamine phosphodiesterase
lysophosphatidic acid