Peripheral Neuronal NPTX2 Exacerbates Chronic Itch in an Atopic Dermatitis Model via Enhancing IL-31/IL-31R Signaling Axis

Peripheral Neuronal NPTX2 Exacerbates Chronic Itch in an Atopic Dermatitis Model via Enhancing IL-31/IL-31R Signaling Axis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 7 June 2025 V1 Latest version Share on Peripheral Neuronal NPTX2 Exacerbates Chronic Itch in an Atopic Dermatitis Model via Enhancing IL-31/IL-31R Signaling Axis Authors : Zhi-Jun Zhang 0000-0001-6996-8683 [email protected] , Xue-Qiang Bai , Bing-Xin Wu , Ji-An Wang , Cheng He , Yong-Liang Shen , Yu-Qi Zhang , Xue-Wen Chen , Rong Sun , Juan Wang , and Xiao Wei Authors Info & Affiliations https://doi.org/10.22541/au.174930124.48420766/v1 333 views 141 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions, primarily characterized by intense itching that leads to scratching and presents a challenging clinical issue with incompletely mechanisms. Neuronal pentraxin 2 (NPTX2) is associated with neurodevelopment, synaptic plasticity, and neuroinflammation in the central nervous system (CNS). This study aimed to thoroughly investigate the peripheral role of NPTX2 in mediating chronic itch under the condition of AD. Experimental Approach Real-time PCR, immunohistochemistry, ELISA assay, Western blot and siRNA intervention were performed to explore the peripheral role of NPTX2 in an Atopic Dermatitis Model. Key Results We demonstrated that NPTX2 was selectively up-regulated in small- and medium-sized trigeminal ganglion (TG) neurons in the MC903-induced AD model, and transported to peripheral nerve terminals. Importantly, protein expression of NPTX2 was significantly elevated in the skin nerves of AD patients. Intriguingly, NPTX2 intradermal administration alone provoked moderate scratching behavior in mice. However, Nptx2 siRNA intra-TG injection significantly attenuated scratching behaviors in AD mice. Mechanistically, NPTX2 synergizes with interleukin-31 (IL-31), a well-known pruritic cytokine in AD, to potentiate p-ERK signaling in primary sensory neurons. PD98059, the inhibitor of p-ERK, significantly alleviated the scratching induced by the combination of NPTX2 and IL-31. Additionally, PD98059 also significantly reduced the up-regulation and release of Nptx2 caused by IL-31 stimulation. Conclusion and Implications Our results offers a new understanding of the molecular mechanisms underlying chronic pruritus in the MC903-induced AD model, for targeting NPTX2-dependent signaling as a key therapeutic strategy for refractory itch disorders. Supplementary Material File (article-figure.docx) Download 8.57 MB File (manuscript.pdf) Download 1.04 MB File (supplementary figure.docx) Download 4.76 MB Information & Authors Information Version history V1 Version 1 07 June 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cytokines histamine immunopharmacology inflammation intercellular signaling skin pharmacology Authors Affiliations Zhi-Jun Zhang 0000-0001-6996-8683 [email protected] Nantong University Medical School View all articles by this author Xue-Qiang Bai Nantong University Medical School View all articles by this author Bing-Xin Wu Nantong University Medical School View all articles by this author Ji-An Wang Shanghai Skin Diseases Hospital View all articles by this author Cheng He Nantong University Medical School View all articles by this author Yong-Liang Shen The Sixth Affiliated Hospital of Nantong University View all articles by this author Yu-Qi Zhang Nantong University Medical School View all articles by this author Xue-Wen Chen Shanghai Skin Diseases Hospital View all articles by this author Rong Sun Nantong University Medical School View all articles by this author Juan Wang Nantong University Medical School View all articles by this author Xiao Wei Nantong University Medical School View all articles by this author Metrics & Citations Metrics Article Usage 333 views 141 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zhi-Jun Zhang, Xue-Qiang Bai, Bing-Xin Wu, et al. Peripheral Neuronal NPTX2 Exacerbates Chronic Itch in an Atopic Dermatitis Model via Enhancing IL-31/IL-31R Signaling Axis. Authorea . 07 June 2025. DOI: https://doi.org/10.22541/au.174930124.48420766/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.174930124.48420766/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a00dfc6e38ede2c5',t:'MTc3OTY0MzM4NA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();