ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus
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...
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doaj-12f23b0701c641e8ad6df83ebc55f7402021-03-04T05:04:36ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-03-01810.3389/fmed.2021.626554626554ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates PruritusXin Jia0Xin Jia1Meng-Han Dai2Meng-Han Dai3An-Jing Ren4Ting-Ting Wang5Ting-Ting Wang6Weiping J. Zhang7Weiping J. Zhang8Ling Zhang9Ling Zhang10The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, ChinaKey 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, ChinaThe First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, ChinaDepartment of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Pathophysiology, Naval Medical University, Shanghai, ChinaThe First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, ChinaDepartment of Dermatology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathophysiology, Naval Medical University, Shanghai, ChinaNHC Key Laboratory of Hormones and Development, Tianjin Institute of Endocrinology, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, ChinaThe First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, ChinaKey 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, ChinaRecent 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.626554/fullitchTRPA1TRPV1ZBTB20trigeminal gangliapain |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin Jia Xin Jia Meng-Han Dai Meng-Han Dai An-Jing Ren Ting-Ting Wang Ting-Ting Wang Weiping J. Zhang Weiping J. Zhang Ling Zhang Ling Zhang |
spellingShingle |
Xin Jia Xin Jia Meng-Han Dai Meng-Han Dai An-Jing Ren Ting-Ting Wang Ting-Ting Wang Weiping J. Zhang Weiping J. Zhang Ling Zhang Ling Zhang ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus Frontiers in Medicine itch TRPA1 TRPV1 ZBTB20 trigeminal ganglia pain |
author_facet |
Xin Jia Xin Jia Meng-Han Dai Meng-Han Dai An-Jing Ren Ting-Ting Wang Ting-Ting Wang Weiping J. Zhang Weiping J. Zhang Ling Zhang Ling Zhang |
author_sort |
Xin Jia |
title |
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus |
title_short |
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus |
title_full |
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus |
title_fullStr |
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus |
title_full_unstemmed |
ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus |
title_sort |
zbtb20 in nociceptive neurons of the trigeminal ganglia regulates pruritus |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2021-03-01 |
description |
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. |
topic |
itch TRPA1 TRPV1 ZBTB20 trigeminal ganglia pain |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2021.626554/full |
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