|
|
Relationship between TRPV1-GRPR-JAK1STAT3 pathway expression and pruritus in allergic contact dermatitis |
TIAN Limin, YANG Sen, LI Wei, A Surui, HUYAN Xiaohui, YANG Yuenan |
Department of Dermatology and Venereology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, China |
|
|
Abstract Objective To investigate Transient receptor potential (TRPV1) - Gastrin releasing peptide receptor, GRPR) -JAK1STAT3 signaling mechanism on skin pruritus in allergic contact dermatitis. Methods The allergic contact dermatitis (ACD) model was induced by dibutyl cubic acid (SADBE) in mice, which were divided into normal group, SADBE group and TRPV1 knockout group. Detect skin thickness and serum immunoglobulin E (IgE). Immunofluorescence and FISH staining were used to detect the expression of Keratin (KRT14), TRPV1 and GRPR in antibody cells, analyze the correlation between their expression and the number of scratches in mice, and fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression of TRPV1-GRPR-JAK1STAT3 signal in the spinal cord of ACD model mice. Results In the mouse ACD model induced by SADBE, prolonged skin itching was observed between 3 and 7 days. Elevated serum IgE levels, thickened epidermis, and increased spleen weight were observed also. Dual FISH studies of lumbar spinal cord sections in mice showed significant overlap between TRPV1 and GRPR, with increased expression of TRPV1, GRPR, JAK1, and STAT3 mRNA in the SADVE group compared with the normal group and decreased expression in the SADBE group after TRPV1 knockout. The number of scratches and epidermal thickness decreased in TRPV1 knockout group, and the difference was statistically significant (P<0.05). Conclusion ACD induced by SADBE resulted in increased pruritus in mice, while inhibition of TRPV1-GRPR-JAK1STAT3 signaling suppressed allergic contact dermatitis skin pruritus.
|
Received: 14 December 2022
|
|
|
|
|
[1] Feng J, Yang P, Mack MR, et al.Sensory TRP channels contribute differentially to skin inflammation and persistent itch[J]. Nat Commun, 2017, 8(1): 980. [2] 王华, 李雅, 汪雯, 梅之南, 等. 麝香草酚对SADBE诱导慢性瘙痒模型小鼠的治疗作用[J]. 时珍国医国药, 2020, 31(04): 831-834. [3] Kittaka H, Tominaga M.The molecular and cellular mechanisms of itch and the involvement of TRP channels in the peripheral sensory nervous system and skin[J]. Allergol Int, 2017, 66: 22-30. [4] 洪安澜, 林彤. TRP通道在炎症性皮肤病中的作用[J]. 中国麻风皮肤病杂志, 2023, 39(2): 129-133. [5] Sun S, Dong X.Trp channels and itch[J]. Semin Immunopathol, 2016, 38: 293-307. [6] Munanairi A, Liu XY, Barry DM, et al.Non-canonical Opioid Signaling Inhibits Itch Transmission in the Spinal Cord of Mice[J]. Cell Rep, 2018, 23(3): 866-877. [7] Guo J, Ba X, Matsuda M, et al.Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System[J]. Front Neurosci, 2020, 14: 581977. [8] Kim J, Kim MG, Jeong SH, et al.STAT3 maintains skin barrier integrity by modulating SPINK5 and KLK5 expression in keratinocytes[J]. Exp Dermatol, 2022, 31(2): 223-232. [9] Cho K, Jang JH, Kim SP, et al.Analysis of Nociceptive Information Encoded in the Temporal Discharge Patterns of Cutaneous C-Fibers[J]. Front Comput Neurosci, 2016, 10: 118. [10] Feng J, Yang P, Mack MR, et al.Sensory TRP channels contribute differentially to skin inflammation and persistent itch[J]. Nat Commun, 2017, 8(1): 980. [11] 王德. 脊髓GRPR和NPRA在过敏性接触性皮炎慢性瘙痒的机制研究[D]. 广州: 广州医科大学, 2020. [12] Kiguchi N, Sukhtankar DD, Ding H, et al.Spinal functions of B-type natriuretic peptide, gastrin-releasing peptide, and their cognate receptors for regulating itch in mice[J]. J Pharmacol Exp Ther, 2016, 356: 596-603. [13] Lee K, Choi YI, Im ST, et al.Riboflavin Inhibits Histamine-Dependent Itch by Modulating Transient Receptor Potential Vanilloid 1(TRPV1)[J]. Front Mol Neurosci, 2021, 14: 643483. [14] Wilson SR.TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch[J]. Nat Neurosci, 2011, 14(5): 595-602. [15] Huang J, Polga´r E, Solinski HJ, et al.Circuit dissection of the role of somatostatin in itch and pain[J]. Nat Neurosci, 2018, 21(6): 894. [16] Welsch K, Holstein J, Laurence A, et al.Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors[J]. Eur J Immunol, 2017, 47(7): 1096-1107. [17] Seavey MM, Dobrzanski P.The many faces of Janus kinase[J]. Biochem Pharmacol, 2012, 83(9): 1136-1145. |
|
|
|