{"id":3616,"date":"2026-01-18T23:24:30","date_gmt":"2026-01-18T14:24:30","guid":{"rendered":"https:\/\/misterx95.myds.me\/wordpress\/?p=3616"},"modified":"2026-01-18T23:24:31","modified_gmt":"2026-01-18T14:24:31","slug":"journal-club-26-1-19","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=3616","title":{"rendered":"Journal club 26.1.19"},"content":{"rendered":"\n<p><strong>Tmem45b modulates itch via endoplasmic reticulum calcium regulation<\/strong><\/p>\n\n\n\n<div class=\"wp-block-file\"><object class=\"wp-block-file__embed\" data=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2026\/01\/Tmem45b-modulates-itch-via-endoplasmic-reticulum-calcium-regulation.pdf\" type=\"application\/pdf\" style=\"width:100%;height:600px\" aria-label=\"Embed of Tmem45b-modulates-itch-via-endoplasmic-reticulum-calcium-regulation.\"><\/object><a id=\"wp-block-file--media-9989097f-52a8-4eea-9f4f-c8e409274464\" href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2026\/01\/Tmem45b-modulates-itch-via-endoplasmic-reticulum-calcium-regulation.pdf\">Tmem45b-modulates-itch-via-endoplasmic-reticulum-calcium-regulation<\/a><a href=\"https:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2026\/01\/Tmem45b-modulates-itch-via-endoplasmic-reticulum-calcium-regulation.pdf\" class=\"wp-block-file__button wp-element-button\" download aria-describedby=\"wp-block-file--media-9989097f-52a8-4eea-9f4f-c8e409274464\">Download<\/a><\/div>\n\n\n\n<p>Sa-shuang Wang1,2,3\u2020, Chen Liang3\u2020, Ruo-lin Wang3, Ze-lin Sun3, Peng-yu Ren3, Bin Wu3, Juan-juan Sun3, Li Fu4, Li-zu Xiao1,Wu-ping Sun1* and Chang-lin Li3,5*<\/p>\n\n\n\n<p>1Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People\u2019s Hospital, and the 6th Affiliated Hospital of Shenzhen University Medical School,Shenzhen, China<\/p>\n\n\n\n<p>\u00a02Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China<\/p>\n\n\n\n<p>3Guangdong Institute of Intelligence Science and Technology, Zhuhai, Guangdong, China<\/p>\n\n\n\n<p>4Guangdong Key Laboratory for Genome Stability and Disease Prevention, Department of Pharmacology and Shenzhen International Cancer Center, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China<\/p>\n\n\n\n<p>5Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an, China<\/p>\n\n\n\n<p>Objective: This study aimed to investigate the role of Tmem45b, a gene expressed in itch-associated Dorsal root ganglion (DRG) neurons, in the regulation of itch sensation.<\/p>\n\n\n\n<p>Methods: The expression of Tmem45b was examined in DRG neurons. These neurons included Nppb-, Mrgpra3-, and Mrgprd-positive subtypes, which are known to mediate itch. Behavioral response to various pruritogens including\u00a0\u03b2-alanine, chloroquine, histamine, serotonin, and N-met-LTC4 were assessed on Mrgprd-cre::Tmem45bflox\/flox\u00a0conditional knockout (cKO) mice. Chronic itch was evaluated using both atopic dermatitis-like and dry skin-like mouse models. To investigate intracellular calcium dynamics, calcium imaging was performed on dissociated DRG neurons. Additionally, bulk RNA-seq was conducted on DRG from Tmem45b cKO mice to assess transcriptomic changes. Serca1 expression and the calcium storage capacity of the endoplasmic reticulum (ER) were analyzed following Tmem45b\u00a0deletion.<\/p>\n\n\n\n<p>Results: Tmem45b was found to be expressed in itch-associated DRG neurons. In Tmem45b cKO mice, scratching behavior was reduced in response to \u03b2-alanine but increased in response to chloroquine. Notably, chronic itch was alleviated in Tmem45b-deficient mice. Calcium imaging revealed that Tmem45b cKO impaired calcium responses to\u00a0\u03b2-alanine and allyl isothiocyanate, but not to chloroquine. Mechanistically, Tmem45b deficiency led to a significant downregulation of Serca1, reducing ER calcium storage capacity. Pharmacological inhibition of Serca1 in DRG neurons similarly suppressed intracellular calcium release in response to\u00a0\u03b2-alanine and chloroquine. <\/p>\n\n\n\n<p>Conclusion: Tmem45b plays a critical role in nonhistaminergic itch by regulating ER calcium homeostasis through Serca1. Its deficiency reduces itch behavior and impairs calcium signaling in DRG neurons, suggesting that Tmem45b is a potential therapeutic target for chronic\u00a0itch.<\/p>\n\n\n\n<p>KEYWORDS : DRG-dorsal root ganglion, itch (pruritus), calcium, endoplasmic reticulum, TMEM45B<\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p>Guangdong, China,&nbsp;5Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an, China<\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tmem45b modulates itch via endoplasmic reticulum calcium regulation Sa-shuang Wang1,2,3\u2020, Chen Liang3\u2020, Ruo-lin Wang3, Ze-lin Sun3, Peng-yu Ren3, Bin Wu3, Juan-juan Sun3, Li Fu4, Li-zu Xiao1,Wu-ping Sun1* and Chang-lin Li3,5* 1Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People\u2019s Hospital, and the 6th Affiliated Hospital of Shenzhen University Medical [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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