MRGPRX4 is a bile acid receptor for human cholestatic itch
- Peking University School of Life Sciences, China
- University of Pennsylvania, United States
- Peking University, China
- Peking University First Hospital, China
- Peking University Third Hospital, China
- Chinese Academy of Sciences, China
- Peking Union Medical College Hospital, China
- Peking-Tsinghua Center for Life Sciences, China
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Department of the Central Committee of the CPC (Junior Thousand Talents Program of China)
- Yulong Li
Chinese Institute for Brain Research (Z181100001518004)
- Yulong Li
University of Pennsylvania (Internal funding)
- Wenqin Luo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All experiments involving human subjects have been approved by institutional review board or ethics committee and the informed consent, and consent to publish, was obtained. Collection of DRG tissue from adult humans was approved by the Committee for Medical Science Research Ethics, Peking University Third Hospital (IRB00006761-2015238), and collection from human embryos was approved by the Reproductive Study Ethics Committee of Peking University Third Hospital (2012SZ-013 and 2017SZ-043) and Beijing Anzhen Hospital (2014012x). The human itch test studies were approved by the Committee for Protecting Human and Animal Subjects at the Department of Psychology, Peking University (#2018-05-02). Collection of blood samples from patients were approved by the Committee for Biomedical Ethics, Peking University First Hospital (2017-R-94).
Reviewing Editor
- David D Ginty, Harvard Medical School, United States
Publication history
- Received: May 13, 2019
- Accepted: September 2, 2019
- Accepted Manuscript published: September 10, 2019 (version 1)
- Version of Record published: October 1, 2019 (version 2)
- Version of Record updated: October 8, 2019 (version 3)
Copyright
© 2019, Yu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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MRGPRX4 is a bile acid receptor for human cholestatic itch
eLife 8:e48431.
https://doi.org/10.7554/eLife.48431
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