MRGPRX4 is a bile acid receptor for human cholestatic itch
Identifieur interne : 004012 ( Main/Exploration ); précédent : 004011; suivant : 004013MRGPRX4 is a bile acid receptor for human cholestatic itch
Auteurs : Huasheng Yu [République populaire de Chine] ; Tianjun Zhao [République populaire de Chine] ; Simin Liu [République populaire de Chine] ; Qinxue Wu [États-Unis] ; Omar Johnson [États-Unis] ; Zhaofa Wu [République populaire de Chine] ; Zihao Zhuang [République populaire de Chine] ; Yaocheng Shi [République populaire de Chine] ; Luxin Peng [République populaire de Chine] ; Renxi He [République populaire de Chine] ; Yong Yang [République populaire de Chine] ; Jianjun Sun [République populaire de Chine] ; Xiaoqun Wang [République populaire de Chine] ; Haifeng Xu [République populaire de Chine] ; Zheng Zeng [République populaire de Chine] ; Peng Zou [République populaire de Chine] ; Xiaoguang Lei [République populaire de Chine] ; Wenqin Luo [États-Unis] ; Yulong Li [République populaire de Chine]Source :
- eLife [ 2050-084X ] ; ????.
Abstract
Patients with liver diseases often suffer from chronic itch, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, we identify bile acids as natural ligands for MRGPRX4. MRGPRX4 is expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with itch receptor HRH1. Bile acids elicited Ca2+ responses in cultured hDRG neurons, and bile acids or a MRGPRX4 specific agonist induced itch in human subjects. However, a specific agonist for another bile acid receptor TGR5 failed to induce itch in human subjects and we find that human TGR5 is not expressed in hDRG neurons. Finally, we show positive correlation between cholestatic itch and plasma bile acids level in itchy patients and the elevated bile acids is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch in human, providing a promising new drug target for anti-itch therapies.
Url:
DOI: 10.7554/eLife.48431
PubMed: 31500698
PubMed Central: 6773440
Affiliations:
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Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Xiaoguang" sort="Lei, Xiaoguang" uniqKey="Lei X" first="Xiaoguang" last="Lei">Xiaoguang Lei</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Peking-Tsinghua Center for Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="dept">Department of Chemical Biology, College of Chemistry and Molecular Engineering</institution><institution>Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Luo, Wenqin" sort="Luo, Wenqin" uniqKey="Luo W" first="Wenqin" last="Luo">Wenqin Luo</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="dept">Department of Neuroscience, Perelman School of Medicine</institution><institution>University of Pennsylvania</institution><addr-line>Philadelphia</addr-line><country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country 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xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Peking-Tsinghua Center for Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Tianjun" sort="Zhao, Tianjun" uniqKey="Zhao T" first="Tianjun" last="Zhao">Tianjun Zhao</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>PKU-IDG/McGovern Institute for Brain Research</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Peking-Tsinghua Center for Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Simin" sort="Liu, Simin" uniqKey="Liu S" first="Simin" last="Liu">Simin Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Qinxue" sort="Wu, Qinxue" uniqKey="Wu Q" first="Qinxue" last="Wu">Qinxue Wu</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="dept">Department of Neuroscience, Perelman School of Medicine</institution><institution>University of Pennsylvania</institution><addr-line>Philadelphia</addr-line><country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Johnson, Omar" sort="Johnson, Omar" uniqKey="Johnson O" first="Omar" last="Johnson">Omar Johnson</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="dept">Department of Neuroscience, Perelman School of Medicine</institution><institution>University of Pennsylvania</institution><addr-line>Philadelphia</addr-line><country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Zhaofa" sort="Wu, Zhaofa" uniqKey="Wu Z" first="Zhaofa" last="Wu">Zhaofa Wu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>PKU-IDG/McGovern Institute for Brain Research</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhuang, Zihao" sort="Zhuang, Zihao" uniqKey="Zhuang Z" first="Zihao" last="Zhuang">Zihao Zhuang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Yaocheng" sort="Shi, Yaocheng" uniqKey="Shi Y" first="Yaocheng" last="Shi">Yaocheng Shi</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="dept">Department of Chemical Biology, College of Chemistry and Molecular Engineering</institution><institution>Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Luxin" sort="Peng, Luxin" uniqKey="Peng L" first="Luxin" last="Peng">Luxin Peng</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="dept">Department of Chemical Biology, College of Chemistry and Molecular Engineering</institution><institution>Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="He, Renxi" sort="He, Renxi" uniqKey="He R" first="Renxi" last="He">Renxi He</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>PKU-IDG/McGovern Institute for Brain Research</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Yong" sort="Yang, Yong" uniqKey="Yang Y" first="Yong" last="Yang">Yong Yang</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution content-type="dept">Department of Dermatology, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses</institution><institution>Peking University First Hospital, Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Jianjun" sort="Sun, Jianjun" uniqKey="Sun J" first="Jianjun" last="Sun">Jianjun Sun</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution content-type="dept">Department of Neurosurgery</institution><institution>Peking University Third Hospital, Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Xiaoqun" sort="Wang, Xiaoqun" uniqKey="Wang X" first="Xiaoqun" last="Wang">Xiaoqun Wang</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution content-type="dept">State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology (Shanghai), Institute of Biophysics</institution><institution>Chinese Academy of Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Haifeng" sort="Xu, Haifeng" uniqKey="Xu H" first="Haifeng" last="Xu">Haifeng Xu</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution content-type="dept">Department of Liver Surgery</institution><institution>Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zeng, Zheng" sort="Zeng, Zheng" uniqKey="Zeng Z" first="Zheng" last="Zeng">Zheng Zeng</name><affiliation wicri:level="1"><nlm:aff id="aff10"><institution content-type="dept">Department of Infectious Diseases</institution><institution>Peking University First Hospital</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zou, Peng" sort="Zou, Peng" uniqKey="Zou P" first="Peng" last="Zou">Peng Zou</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="dept">Department of Chemical Biology, College of Chemistry and Molecular Engineering</institution><institution>Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lei, Xiaoguang" sort="Lei, Xiaoguang" uniqKey="Lei X" first="Xiaoguang" last="Lei">Xiaoguang Lei</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Peking-Tsinghua Center for Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="dept">Department of Chemical Biology, College of Chemistry and Molecular Engineering</institution><institution>Peking University</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Luo, Wenqin" sort="Luo, Wenqin" uniqKey="Luo W" first="Wenqin" last="Luo">Wenqin Luo</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="dept">Department of Neuroscience, Perelman School of Medicine</institution><institution>University of Pennsylvania</institution><addr-line>Philadelphia</addr-line><country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="dept">State Key Laboratory of Membrane Biology</institution><institution>Peking University School of Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>PKU-IDG/McGovern Institute for Brain Research</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Peking-Tsinghua Center for Life Sciences</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff11"><institution>Chinese Institute for Brain Research</institution><addr-line>Beijing</addr-line><country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">eLife</title><idno type="eISSN">2050-084X</idno><imprint><date when="????">????</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Patients with liver diseases often suffer from chronic itch, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, we identify bile acids as natural ligands for MRGPRX4. MRGPRX4 is expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with itch receptor HRH1. Bile acids elicited Ca<sup>2+</sup> responses in cultured hDRG neurons, and bile acids or a MRGPRX4 specific agonist induced itch in human subjects. However, a specific agonist for another bile acid receptor TGR5 failed to induce itch in human subjects and we find that human TGR5 is not expressed in hDRG neurons. Finally, we show positive correlation between cholestatic itch and plasma bile acids level in itchy patients and the elevated bile acids is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch in human, providing a promising new drug target for anti-itch therapies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alemi, F" uniqKey="Alemi F">F Alemi</name></author><author><name sortKey="Kwon, E" uniqKey="Kwon E">E Kwon</name></author><author><name sortKey="Poole, Dp" uniqKey="Poole D">DP Poole</name></author><author><name sortKey="Lieu, T" uniqKey="Lieu T">T Lieu</name></author><author><name sortKey="Lyo, V" uniqKey="Lyo V">V Lyo</name></author><author><name sortKey="Cattaruzza, F" uniqKey="Cattaruzza F">F Cattaruzza</name></author><author><name sortKey="Cevikbas, F" uniqKey="Cevikbas F">F Cevikbas</name></author><author><name sortKey="Steinhoff, M" uniqKey="Steinhoff M">M Steinhoff</name></author><author><name sortKey="Nassini, R" uniqKey="Nassini R">R Nassini</name></author><author><name 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Chine</li><li>États-Unis</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Yu, Huasheng" sort="Yu, Huasheng" uniqKey="Yu H" first="Huasheng" last="Yu">Huasheng Yu</name></noRegion><name sortKey="He, Renxi" sort="He, Renxi" uniqKey="He R" first="Renxi" last="He">Renxi He</name><name sortKey="He, Renxi" sort="He, Renxi" uniqKey="He R" first="Renxi" last="He">Renxi He</name><name sortKey="Lei, Xiaoguang" sort="Lei, Xiaoguang" uniqKey="Lei X" first="Xiaoguang" last="Lei">Xiaoguang Lei</name><name sortKey="Lei, Xiaoguang" sort="Lei, Xiaoguang" uniqKey="Lei X" first="Xiaoguang" last="Lei">Xiaoguang Lei</name><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><name sortKey="Li, Yulong" sort="Li, Yulong" uniqKey="Li Y" first="Yulong" last="Li">Yulong Li</name><name sortKey="Liu, Simin" sort="Liu, Simin" uniqKey="Liu S" first="Simin" last="Liu">Simin Liu</name><name sortKey="Peng, Luxin" sort="Peng, Luxin" uniqKey="Peng L" first="Luxin" last="Peng">Luxin Peng</name><name sortKey="Shi, Yaocheng" sort="Shi, Yaocheng" uniqKey="Shi Y" first="Yaocheng" last="Shi">Yaocheng Shi</name><name sortKey="Sun, Jianjun" sort="Sun, Jianjun" uniqKey="Sun J" first="Jianjun" last="Sun">Jianjun Sun</name><name sortKey="Wang, Xiaoqun" sort="Wang, Xiaoqun" uniqKey="Wang X" first="Xiaoqun" last="Wang">Xiaoqun Wang</name><name sortKey="Wu, Zhaofa" sort="Wu, Zhaofa" uniqKey="Wu Z" first="Zhaofa" last="Wu">Zhaofa Wu</name><name sortKey="Wu, Zhaofa" sort="Wu, Zhaofa" uniqKey="Wu Z" first="Zhaofa" last="Wu">Zhaofa Wu</name><name sortKey="Xu, Haifeng" sort="Xu, Haifeng" uniqKey="Xu H" first="Haifeng" last="Xu">Haifeng Xu</name><name sortKey="Yang, Yong" sort="Yang, Yong" uniqKey="Yang Y" first="Yong" last="Yang">Yong Yang</name><name sortKey="Yu, Huasheng" sort="Yu, Huasheng" uniqKey="Yu H" first="Huasheng" last="Yu">Huasheng Yu</name><name sortKey="Yu, Huasheng" sort="Yu, Huasheng" uniqKey="Yu H" first="Huasheng" last="Yu">Huasheng Yu</name><name sortKey="Zeng, Zheng" sort="Zeng, Zheng" uniqKey="Zeng Z" first="Zheng" last="Zeng">Zheng Zeng</name><name sortKey="Zhao, Tianjun" sort="Zhao, Tianjun" uniqKey="Zhao T" first="Tianjun" last="Zhao">Tianjun Zhao</name><name sortKey="Zhao, Tianjun" sort="Zhao, Tianjun" uniqKey="Zhao T" first="Tianjun" last="Zhao">Tianjun Zhao</name><name sortKey="Zhao, Tianjun" sort="Zhao, Tianjun" uniqKey="Zhao T" first="Tianjun" last="Zhao">Tianjun Zhao</name><name sortKey="Zhuang, Zihao" sort="Zhuang, Zihao" uniqKey="Zhuang Z" first="Zihao" last="Zhuang">Zihao Zhuang</name><name sortKey="Zou, Peng" sort="Zou, Peng" uniqKey="Zou P" first="Peng" last="Zou">Peng Zou</name></country><country name="États-Unis"><noRegion><name sortKey="Wu, Qinxue" sort="Wu, Qinxue" uniqKey="Wu Q" first="Qinxue" last="Wu">Qinxue Wu</name></noRegion><name sortKey="Johnson, Omar" sort="Johnson, Omar" uniqKey="Johnson O" first="Omar" last="Johnson">Omar Johnson</name><name sortKey="Luo, Wenqin" sort="Luo, Wenqin" uniqKey="Luo W" first="Wenqin" last="Luo">Wenqin Luo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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