PMID- 33748159 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210323 IS - 2296-858X (Print) IS - 2296-858X (Electronic) IS - 2296-858X (Linking) VI - 8 DP - 2021 TI - ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus. PG - 626554 LID - 10.3389/fmed.2021.626554 [doi] LID - 626554 AB - Recent studies have shown that ZBTB20, a zinc-finger protein containing transcription factor, is highly expressed in small-diameter primary sensory neurons in mice, and modulates pain through regulating TRP channels. However, whether ZBTB20 regulates itch sensation has not been demonstrated. In this study, small-diameter primary sensory neuron-specific ZBTB20 knockout (PN-ZB20KO) mice were used to investigate the role of ZBTB20 in the regulation of itch sensation. First, both histamine-dependent and non-histamine-dependent itch behaviors induced by injection of histamine and chloroquine (CQ) into the cheek were significantly diminished in PN-ZB20KO mice. Second, double immunohistochemistry showed that ZBTB20 was mainly expressed in CGRP-labeled small peptidergic neurons and was expressed at low levels in IB4-labeled small non-peptidergic and NF200-labeled large neurons in the trigeminal ganglia (TG). ZBTB20 was also expressed in most TRPV1(+) and TRPA1(+) neurons and to a lesser extent in TRPM8(+) neurons in the TG. Furthermore, cheek injection of histamine and CQ enhanced the mRNA expression of TRPV1 and TRPA1 but not TRPM8 in the TG. Moreover, TRPV1 and TRPA1 knockout (KO) mice exhibited attenuation of itch behavior induced by histamine and CQ, respectively. Finally, silencing endogenous ZBTB20 with recombinant lentivirus expressing a short hairpin RNA against ZBTB20 (LV-shZBTB20) in TG neurons attenuated histamine- and non-histamine-induced itch and downregulated TRP channels in the TG. Our study suggests that ZBTB20 plays an important role in mediating itch in small primary sensory neurons. CI - Copyright (c) 2021 Jia, Dai, Ren, Wang, Zhang and Zhang. FAU - Jia, Xin AU - Jia X AD - The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China. AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Dai, Meng-Han AU - Dai MH AD - The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China. AD - Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, China. FAU - Ren, An-Jing AU - Ren AJ AD - Department of Pathophysiology, Naval Medical University, Shanghai, China. FAU - Wang, Ting-Ting AU - Wang TT AD - The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China. AD - Department of Dermatology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhang, Weiping J AU - Zhang WJ AD - Department of Pathophysiology, Naval Medical University, Shanghai, China. AD - NHC Key Laboratory of Hormones and Development, Tianjin Institute of Endocrinology, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, China. FAU - Zhang, Ling AU - Zhang L AD - The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China. AD - Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, Tongji University, Shanghai, China. LA - eng PT - Journal Article DEP - 20210304 PL - Switzerland TA - Front Med (Lausanne) JT - Frontiers in medicine JID - 101648047 PMC - PMC7969640 OTO - NOTNLM OT - TRPA1 OT - TRPV1 OT - ZBTB20 OT - itch OT - pain OT - pruritus OT - trigeminal ganglia COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/23 06:00 MHDA- 2021/03/23 06:01 PMCR- 2021/03/04 CRDT- 2021/03/22 08:22 PHST- 2020/11/06 00:00 [received] PHST- 2021/01/11 00:00 [accepted] PHST- 2021/03/22 08:22 [entrez] PHST- 2021/03/23 06:00 [pubmed] PHST- 2021/03/23 06:01 [medline] PHST- 2021/03/04 00:00 [pmc-release] AID - 10.3389/fmed.2021.626554 [doi] PST - epublish SO - Front Med (Lausanne). 2021 Mar 4;8:626554. doi: 10.3389/fmed.2021.626554. eCollection 2021.