Jia Xin, Dai Meng-Han, Ren An-Jing, Wang Ting-Ting, Zhang Weiping J, Zhang Ling
The First Rehabilitation Hospital of Shanghai, Tongji University School of Medicine, Shanghai, China.
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.
Front Med (Lausanne). 2021 Mar 4;8:626554. doi: 10.3389/fmed.2021.626554. eCollection 2021.
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.
最近的研究表明，锌指蛋白转录因子ZBTB20在小鼠小直径初级感觉神经元中高表达，并通过调节瞬时受体电位（TRP）通道来调节疼痛。然而，ZBTB20是否调节瘙痒感觉尚未得到证实。在本研究中，使用小直径初级感觉神经元特异性ZBTB20基因敲除（PN-ZB20KO）小鼠来研究ZBTB20在瘙痒感觉调节中的作用。首先，向脸颊注射组胺和氯喹（CQ）诱导的组胺依赖性和非组胺依赖性瘙痒行为在PN-ZB20KO小鼠中均显著减弱。其次，双重免疫组化显示，ZBTB20主要表达于降钙素基因相关肽（CGRP）标记的小肽能神经元中，在三叉神经节（TG）中IB4标记的小非肽能神经元和NF200标记的大神经元中低表达。ZBTB20在TG中的大多数TRPV1和TRPA1神经元中也有表达，而在TRPM8神经元中的表达程度较低。此外，向脸颊注射组胺和CQ可增强TG中TRPV1和TRPA1的mRNA表达，但不增强TRPM8的表达。此外，TRPV1和TRPA1基因敲除（KO）小鼠分别表现出组胺和CQ诱导的瘙痒行为减弱。最后，在TG神经元中用表达针对ZBTB20的短发夹RNA的重组慢病毒（LV-shZBTB20）沉默内源性ZBTB20可减弱组胺和非组胺诱导的瘙痒，并下调TG中的TRP通道。我们的研究表明，ZBTB20在介导小初级感觉神经元的瘙痒中起重要作用。
