title: Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC).
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.
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Weici
authors.initials: W
authors.lastname: Zhang
authors.affiliation: PharmAkea Therapeutics, San Diego, California, USA. Electronic address: jevans@pharmakea.com.
authors.forename: Jilly F
authors.initials: JF
authors.lastname: Evans
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy. Electronic address: annarosa.floreani@unipd.it.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Floreani
authors.affiliation: Center for the Treatment and Research of Non-Infectious Liver Diseases, Beijing 302 Hospital, Beijing, 100039, China. Electronic address: zszou302@163.com.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zou
authors.affiliation: 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.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishio
authors.affiliation: Department of General Surgery, Beijing 302nd Hospital, Beijing, 10039, China. Electronic address: rzhqi@sina.com.
authors.forename: Ruizhao
authors.initials: R
authors.lastname: Qi
authors.affiliation: 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.
authors.forename: Patrick S C
authors.initials: PS
authors.lastname: Leung
authors.affiliation: Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Davis, California, USA. Electronic address: clbowlus@ucdavis.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bowlus
authors.affiliation: 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.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways; D002761:Cholangitis / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000096:biosynthesis*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011537:Pruritus / Q000378:metabolism*; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid
keywords: Autotaxin; autoimmunity; cholestatic liver diseases; lysophosphatidylcholine; pruritus