Upregulation of DRG protein TMEM100 facilitates dry skin-induced pruritus by enhancing TRPA1 channel function  

作　　者：Chao Pan Yingfu Jiao Dexu Kong Haoyue Deng Saihong Xu Dan Tang Wen Yin Po Gao Weifeng Yu Yinghui Fan Daxiang Wen 

机构地区：[1]Department of Anesthesiology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第3期404-416,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(No.81970478 to D.W.and No.82101290 to W.Y.);the Shanghai Municipal Health Commission Healthcare Industry Clinical Research Special Fund of 2019(No.201940034 to Y.F.);the Shanghai Science and Technology Commission Medical Innovation Research Special Fund(No.19411951900 to D.W.and No.21Y11906000 to Y.F.);the Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai(No.PWZXQ2017-06);the Shanghai Municipal Key Clinical Specialty(No.shslczdzk03601);the Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation(No.20DZ2254200);the Innovative Research Team of High-level Local Universities in Shanghai(No.SHSMU-ZDCX20211102 to Y.J.).

摘　　要：The dry skin tortures numerous patients with severe itch.The transient receptor potential cation channel V member 1(TRPV1)and A member 1(TRPA1)are two essential receptors for peripheral neural coding of itch sensory,mediating histaminergic and nonhistaminergic itch separately.In the dorsal root ganglion,transmembrane protein 100(TMEM100)is structurally related to both TRPV1 and TRPA1 receptors,but the exact role of TMEM100 in itch sensory coding is still unknown.Here,in this study,we find that TMEM100+DRG neurons account for the majority of activated neurons in an acetone-ether-water(AEW)-induced dry skin itch model,and some TMEM100+DRG neurons are colocalized with both TRPA1 and the chloroquine-related Mrgpr itch receptor family.Both the expression and function of TRPA1 channels,but not TRPV1 channels,are upregulated in the AEW model,and specific DRGTmem100 gene knockdown alleviates AEW-induced itch and rescues the expression and functional changes of TRPA1.Our results strongly suggest that TMEM100 protein in DRG is the main facilitating factor for dry skin-related chronic itch,and specific suppression of TMEM100 in DRG could be a novel effective treatment strategy for patients who suffer from dry skin-induced itch.

关 键 词：dry skin-induced itch TMEM100 TRPA1 TRPV1 DRG 

分 类 号：R758.3+1[医药卫生—皮肤病学与性病学]