皮肤触觉感受器默克尔细胞功能研究进展

袁绘普; 丁圆圆; 郑懿欣; 张雅君; 刘霞; 芮晨; 王超尘; 肖瑛

doi:10.3760/cma.j.cn501120-20211209-00409

皮肤触觉感受器默克尔细胞功能研究进展

doi: 10.3760/cma.j.cn501120-20211209-00409

1.
浙江大学医学院附属邵逸夫医院生物医学研究中心，杭州　　310020
2.
中国科学院上海药物研究所安全评价研究中心，上海　　201203
3.
浙江大学爱丁堡大学联合学院，海宁　　314400

基金项目:

国家自然科学基金面上项目 32070816

浙江省自然科学基金 LQ22C070002

详细信息

通讯作者:
肖瑛，Email：xiaoying.srr@zju.edu.cn

计量
- 文章访问数: 248
- HTML全文浏览量: 98
- PDF下载量: 28
- 被引次数: 0
出版历程
- 收稿日期: 2021-12-09

Research advances on the function of skin touch receptor Merkel cells

1.
Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310020, China
2.
Centre for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China
3.
Union College of Edinburgh University, Zhejiang University, Haining 314400, China

Funds:

General Program of National Natural Science Foundation of China 32070816

Natural Science Foundation of Zhejiang Province of China LQ22C070002

More Information

Corresponding author: Xiao Ying, Email: xiaoying.srr@zju.edu.cn

摘要

摘要: 在由烧伤等因素导致的皮肤损伤修复过程中，触觉功能的重建离不开触觉感受器默克尔细胞的功能再生。默克尔细胞主要存在于表皮基底层，与神经紧密相连形成默克尔细胞-神经复合体，在生物机体内发挥重要作用。大量研究表明默克尔细胞通过机械门控离子通道PIEZO2对机械力刺激进行精确传导，行使触觉感受器的功能。该文通过论述默克尔细胞的特征，分析该类细胞可能存在的不同亚群及其功能，同时调研了触觉相关疾病的动物模型研究和触觉相关的临床疾病，揭示了默克尔细胞功能研究的重要性。
- 皮肤 /
- 默克尔细胞 /
- 触觉 /
- 感受器 /
- PIEZO2
Abstract: The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.
- Skin /
- Merkel cells /
- Touch /
- Sensilla /
- PIEZO2
所有作者均声明不存在利益冲突

HTML全文

1 默克尔细胞形态特征示意图

下载: 全尺寸图片幻灯片

参考文献(46)

[1]	XiaoY,WilliamsJS,BrownellI.Merkel cells and touch domes: more than mechanosensory functions?[J].Exp Dermatol,2014,23(10):692-695.DOI: 10.1111/exd.12456.
[2]	EispertAC,FuchsF,BrandnerJM,et al.Evidence for distinct populations of human Merkel cells[J].Histochem Cell Biol,2009,132(1):83-93.DOI: 10.1007/s00418-009-0578-0.
[3]	LucarzA,BrandG.Current considerations about Merkel cells[J].Eur J Cell Biol,2007,86(5):243-251.DOI: 10.1016/j.ejcb.2007.02.001.
[4]	WooSH,RanadeS,WeyerAD,et al.Piezo2 is required for Merkel-cell mechanotransduction[J].Nature,2014,509(7502):622-626.DOI: 10.1038/nature13251.
[5]	CárcabaL,García-PiquerasJ,García-MesaY,et al.Human digital merkel cells display pannexin1 immunoreactivity[J].Ann Anat,2022,239:151813.DOI: 10.1016/j.aanat.2021.151813.
[6]	NguyenMB,ValdesVJ,CohenI,et al.Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2-mediated signalling[J].Exp Dermatol,2019,28(4):374-382.DOI: 10.1111/exd.13901.
[7]	HaeberleH,FujiwaraM,ChuangJ,et al.Molecular profiling reveals synaptic release machinery in Merkel cells[J].Proc Natl Acad Sci U S A,2004,101(40):14503-14508.DOI: 10.1073/pnas.0406308101.
[8]	HoffmanBU,BabaY,GriffithTN,et al.Merkel cells activate sensory neural pathways through adrenergic synapses[J].Neuron,2018,100(6):1401-1413.e6.DOI: 10.1016/j.neuron.2018.10.034.
[9]	游兴,魏在荣.默克尔细胞在皮肤触觉形成中的作用研究进展[J].中华烧伤杂志,2018,34(1):51-54.DOI: 10.3760/cma.j.issn.1009-2587.2018.01.010.
[10]	García-MesaY,García-PiquerasJ,GarcíaB,et al.Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity[J].J Anat,2017,231(6):978-989.DOI: 10.1111/joa.12688.
[11]	ZimmermanA,BaiL,GintyDD.The gentle touch receptors of mammalian skin[J].Science,2014,346(6212):950-954.DOI: 10.1126/science.1254229.
[12]	IkedaR,ChaM,LingJ,et al.Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses[J].Cell,2014,157(3):664-675.DOI: 10.1016/j.cell.2014.02.026.
[13]	ChangW,GuJG.Effects on tactile transmission by serotonin transporter inhibitors at Merkel discs of mouse whisker hair follicles[J].Mol Pain,2020,16:1744806920938237.DOI: 10.1177/1744806920938237.
[14]	HonoréE,MartinsJR,PentonD,et al.The Piezo mechanosensitive ion channels: may the force be with you![J].Rev Physiol Biochem Pharmacol,2015,169:25-41.DOI: 10.1007/112_2015_26.
[15]	FengJ,LuoJ,YangP,et al.Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch[J].Science,2018,360(6388):530-533.DOI: 10.1126/science.aar5703.
[16]	CotsarelisG,SunTT,LavkerRM.Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis[J].Cell,1990,61(7):1329-1337.DOI: 10.1016/0092-8674(90)90696-c.
[17]	FantiniF,JohanssonO.Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation[J].Exp Dermatol,1995,4(6):365-371.DOI: 10.1111/j.1600-0625.1995.tb00061.x.
[18]	MahmudAA,NahidNA,NassifC,et al.Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures[J].Clin Genet,2017,91(3):470-475.DOI: 10.1111/cge.12850.
[19]	HeCX,CantuDA,MantriSS,et al.Tactile defensiveness and impaired adaptation of neuronal activity in the fmr1 knock-out mouse model of autism[J].J Neurosci,2017,37(27):6475-6487.DOI: 10.1523/JNEUROSCI.0651-17.2017.
[20]	ZhangY,BonnanA,BonyG,et al.Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(-/y) mice[J].Nat Neurosci,2014,17(12):1701-1709.DOI: 10.1038/nn.3864.
[21]	SchafflerMD,MiddletonLJ,Abdus-SaboorI.Mechanisms of tactile sensory phenotypes in autism: current understanding and future directions for research[J].Curr Psychiatry Rep,2019,21(12):134.DOI: 10.1007/s11920-019-1122-0.
[22]	HanQ,KimYH,WangX,et al.SHANK3 deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons[J].Neuron,2016,92(6):1279-1293.DOI: 10.1016/j.neuron.2016.11.007.
[23]	WangX,BeyAL,KatzBM,et al.Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism[J].Nat Commun,2016,7:11459.DOI: 10.1038/ncomms11459.
[24]	MashayekhiF,MizbanN,BidabadiE,et al.The association of SHANK3 gene polymorphism and autism[J].Minerva Pediatr (Torino),2021,73(3):251-255.DOI: 10.23736/S2724-5276.16.04539-4.
[25]	OreficeLL,ZimmermanAL,ChirilaAM,et al.Peripheral mechanosensory neuron dysfunction underlies tactile and behavioral deficits in mouse models of ASDs[J].Cell,2016,166(2):299-313.DOI: 10.1016/j.cell.2016.05.033.
[26]	PratoV,TabernerFJ,HockleyJRF,et al.Functional and molecular characterization of mechanoinsensitive "silent" nociceptors[J].Cell Rep,2017,21(11):3102-3115.DOI: 10.1016/j.celrep.2017.11.066.
[27]	MoehringF,HalderP,SealRP,et al.Uncovering the cells and circuits of touch in normal and pathological settings[J].Neuron,2018,100(2):349-360.DOI: 10.1016/j.neuron.2018.10.019.
[28]	JeonSM,ChangD,GeskeA,et al.Sex-dependent reduction in mechanical allodynia in the sural-sparing nerve injury model in mice lacking Merkel cells[J].J Neurosci,2021,41(26):5595-5619.DOI: 10.1523/JNEUROSCI.1668-20.2021.
[29]	García-MesaY,FeitoJ,González-GayM,et al.Involvement of cutaneous sensory corpuscles in non-painful and painful diabetic neuropathy[J].J Clin Med,2021,10(19):4609.DOI: 10.3390/jcm10194609.
[30]	ZhaoP,BarrTP,HouQ,et al.Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain[J].Pain,2008,139(1):90-105.DOI: 10.1016/j.pain.2008.03.016.
[31]	FellGL,RobinsonKC,MaoJ,et al.Skin β-endorphin mediates addiction to UV light[J].Cell,2014,157(7):1527-1534.DOI: 10.1016/j.cell.2014.04.032.
[32]	MooreC,CevikbasF,PasolliHA,et al.UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling[J].Proc Natl Acad Sci U S A,2013,110(34):E3225-3234.DOI: 10.1073/pnas.1312933110.
[33]	ByunHJ,JangD,LeeDY,et al.Immunohistochemical analysis of prurigo nodularis in 209 patients: clinicopathological analysis between atopic and non-atopic patients and between treatment response groups[J].Ann Dermatol,2021,33(4):333-338.DOI: 10.5021/ad.2021.33.4.333.
[34]	García-PiquerasJ,García-MesaY,CárcabaL,et al.Ageing of the somatosensory system at the periphery: age-related changes in cutaneous mechanoreceptors[J].J Anat,2019,234(6):839-852.DOI: 10.1111/joa.12983.
[35]	MeirteJ,MoortgatP,TruijenS,et al.Interrater and intrarater reliability of the Semmes Weinstein aesthesiometer to assess touch pressure threshold in burn scars[J].Burns,2015,41(6):1261-1267.DOI: 10.1016/j.burns.2015.01.003.
[36]	BanachM,JuranekJK,ZygulskaAL.Chemotherapy-induced neuropathies-a growing problem for patients and health care providers[J].Brain Behav,2016,7(1):e00558.DOI: 10.1002/brb3.558.
[37]	ChangW,GuJG.Impairment of tactile responses and Piezo2 channel mechanotransduction in mice following chronic vincristine treatment[J].Neurosci Lett,2019,705:14-19.DOI: 10.1016/j.neulet.2019.03.045.
[38]	QuintalI,CarrierA,PackhamT,et al.Tactile stimulation programs in patients with hand dysesthesia after a peripheral nerve injury: a systematic review[J].J Hand Ther,2021,34(1):3-17.DOI: 10.1016/j.jht.2020.05.003.
[39]	KrimmRF,DavisBM,AlbersKM.Cutaneous overexpression of neurotrophin-3 (NT3) selectively restores sensory innervation in NT3 gene knockout mice[J].J Neurobiol,2000,43(1):40-49.DOI: 10.1002/(sici)1097-4695(200004)43:1<40::aid-neu4>3.0.co;2-r.
[40]	HahnJM,CombsKA,LloydCM,et al.Identification of Merkel cells associated with neurons in engineered skin substitutes after grafting to full thickness wounds[J].PLoS One,2019,14(3):e0213325.DOI: 10.1371/journal.pone.0213325.
[41]	BlaisM,GrenierM,BerthodF.Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells[J].J Invest Dermatol,2009,129(12):2895-2900.DOI: 10.1038/jid.2009.159.
[42]	DoucetYS,WooSH,RuizME,et al.The touch dome defines an epidermal niche specialized for mechanosensory signaling[J].Cell Rep,2013,3(6):1759-1765.DOI: 10.1016/j.celrep.2013.04.026.
[43]	杨涛,陈佳,成贝贝,等.穿支皮瓣联合足趾移植术修复拇指毁损伴手部软组织缺损的临床疗效[J].中华烧伤杂志,2021,37(9):875-879.DOI: 10.3760/cma.j.cn501120-20200727-00360.
[44]	NetscherD,ArmentaAH,MeadeRA,et al.Sensory recovery of innervated and non-innervated radial forearm free flaps: functional implications[J].J Reconstr Microsurg,2000,16(3):179-185.DOI: 10.1055/s-2000-7549.
[45]	MurrayRZ,WestZE,CowinAJ,et al.Development and use of biomaterials as wound healing therapies[J/OL].Burns Trauma,2019,7:2[2021-12-09].https://pubmed.ncbi.nlm.nih.gov/30701184/.DOI: 10.1186/s41038-018-0139-7.
[46]	SzczotM,LiljencrantzJ,GhitaniN,et al.PIEZO2 mediates injury-induced tactile pain in mice and humans[J].Sci Transl Med,2018,10(462):eaat9892.DOI: 10.1126/scitranslmed.aat9892.