Autotaxin, Pruritus and Primary Biliary Cholangitis (PBC)

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• 作者：Ying Sun^a ; ^b ; ^{sunying_302@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Weici Zhang^a ; ^{ddzhang@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author} ; Jilly F. Evans^c ; ^{jevans@pharmakea.com" class="auth_mail" title="E-mail the corresponding author} ; Annarosa Floreani^d ; ^{annarosa.floreani@unipd.it" class="auth_mail" title="E-mail the corresponding author} ; Zhengsheng Zou^b ; ^{zszou302@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yukiko Nishio^a ; ^{yukiko.n.naramed@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Ruizhao Qi^e ; ^{rzhqi@sina.com" class="auth_mail" title="E-mail the corresponding author} ; Patrick S.C. Leung^a ; ^{psleung@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author} ; Christopher L. Bowlus^f ; ^{clbowlus@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author} ; M. Eric Gershwin^a ; ^{megershwin@ucdavis.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Autotaxin ; lysophosphatidylcholine ; cholestatic liver diseases ; pruritus ; autoimmunity
• 刊名：Autoimmunity Reviews
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：15
• 期：8
• 页码：795-800
• 全文大小：707 K

文摘

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.