Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms.
Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms.
复制标题
DOI：
10.1016/j.pain.2011.04.033
复制
发表时间：
2011-09
期刊：
影响因子：
7.4
通讯作者：
Albrecht P
中科院分区：
文献类型：
--
作者：
Hou Q;Barr T;Gee L;Vickers J;Wymer J;Borsani E;Rodella L;Getsios S;Burdo T;Eisenberg E;Guha U;Lavker R;Kessler J;Chittur S;Fiorino D;Rice F;Albrecht P
降钙素基因相关肽（CGRP）是一种血管舒张肽，在各种炎症和慢性疼痛条件下，在皮肤、血液和脑脊液中检测到高水平，推测来源于肽能C和Aδ神经支配。本文中，在表皮角质形成细胞中检测到CGRP免疫标记（IL），其水平在患有带状疱疹后神经痛（PHN）和1型复杂区域疼痛综合征（CRPS）的人的皮肤中、感染猿猴免疫缺陷病毒的猴的皮肤中、以及经历L5/L 6脊神经结扎、坐骨神经慢性收缩、并皮下注射完全弗氏佐剂。在具有角蛋白-14启动子驱动的头蛋白（BMP-4信号传导的拮抗剂）过表达的转基因小鼠的表皮角化细胞中也检测到CGRP-IL增加。转录组微阵列、qPCR和Western印迹分析使用来自转基因、人和小鼠角质形成细胞的单层培养物和多层人角质形成细胞器官型培养物的激光捕获的小鼠表皮，揭示角质形成细胞主要表达CGRP的β同种型。皮肤肽能神经支配已显示主要表达CGRP的α同种型。角质形成细胞还表达同源CGRP受体组分CRLR、RAMP 1和RCP，这与CGRP促进角质形成细胞中的几种功能变化（包括增殖和细胞因子产生）的已知观察结果一致。我们的研究结果表明，角质形成细胞来源的CGRPβ可能通过自分泌/旁分泌信号调节表皮稳态，并可能在病理条件下导致慢性疼痛。
Calcitonin Gene-Related Peptide (CGRP) is a vasodilatory peptide that has been detected at high levels in the skin, blood, and cerebral spinal fluid under a variety of inflammatory and chronic pain conditions, presumably derived from peptidergic C and Aδ innervation. Herein, CGRP immunolabeling (IL) was detected in epidermal keratinocytes at levels that were especially high and widespread in the skin of humans from locations afflicted with postherpetic neuralgia (PHN) and complex region pain syndrome type 1 (CRPS), of monkeys infected with simian immunodeficiency virus, and of rats subjected to L5/L6 spinal nerve ligation, sciatic nerve chronic constriction, and subcutaneous injection of Complete Freund’s Adjuvant. Increased CGRP-IL was also detected in epidermal keratinocytes of transgenic mice with keratin-14 promoter driven overexpression of noggin, an antagonist to BMP-4 signaling. Transcriptome microarray, qPCR, and Western blot analyses using laser captured mouse epidermis from transgenics, monolayer cultures of human and mouse keratinocytes, and multilayer human keratinocyte organotypic cultures, revealed that keratinocytes express predominantly the beta isoform of CGRP. Cutaneous peptidergic innervation has been shown to express predominantly the alpha isoform of CGRP. Keratinocytes also express the cognate CGRP receptor components, CRLR, RAMP1, and RCP, consistent with known observations that CGRP promotes several functional changes in keratinocytes, including proliferation and cytokine production. Our results indicate that keratinocyte derived CGRPβ may modulate epidermal homeostasis through autocrine/paracrine signaling and may contribute to chronic pain under pathological conditions.
登录
查看更多内容
影响因子：
3.6
作者：
Denda, Mitsuhiro;Tsutsumi, Moe;Denda, Sumiko
通讯作者：
Denda, Sumiko
影响因子：
2.9
作者：
CRIDLAND, RA;HENRY, JL
通讯作者：
HENRY, JL
影响因子：
5.3
作者：
Akopian, Armen N.;Ruparel, Nikita B.;Hargreaves, Kenneth M.
通讯作者：
Hargreaves, Kenneth M.
影响因子：
7.4
作者：
Cannon, Keri E.;Chazot, Paul L.;Rice, Frank L.
通讯作者：
Rice, Frank L.
影响因子：
4.8
作者：
Chung, MK;Lee, H;Caterina, MJ
通讯作者：
Caterina, MJ