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Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms.

Pain. 2011 Sep;152(9):2036-2051. Epub 2011 Jun 17
Quanzhi Hou 1 , Travis Barr , Lucy Gee , Jeff Vickers , James Wymer , Elisa Borsani , Luigi Rodella , Spiro Getsios , Trisha Burdo , Elan Eisenberg , Udayan Guha , Robert Lavker , John Kessler , Sridar Chittur , Dennis Fiorino , Frank Rice , Phillip Albrecht
Quanzhi Hou 1 , Travis Barr , Lucy Gee , Jeff Vickers , James Wymer , Elisa Borsani , Luigi Rodella , Spiro Getsios , Trisha Burdo , Elan Eisenberg , Udayan Guha , Robert Lavker , John Kessler , Sridar Chittur , Dennis Fiorino , Frank Rice , Phillip Albrecht
+ et al

[No authors listed]

Author information
  • 1 Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY, USA Department of Neurology, Albany Medical College, Albany, NY, USA Division of Human Anatomy, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Department of Biology, Boston College, Chestnut Hill, MA, USA Rambam Medical Center, Faculty of Medicine, Israel Institute of Technology, Haifa, Israel Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Center for Functional Genomics, SUNY Albany, Rensselaer, NY, USA In Vivo Pharmacology, Vertex Pharmaceuticals, San Diego, CA, USA Integrated Tissue Dynamics, LLC, Rensselaer, NY, USA.

摘要


Calcitonin gene-related peptide (CGRP) is a vasodilatory peptide that has been detected at high levels in the skin, blood, and cerebrospinal fluid (CSF) 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, quantitative (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, Calcitonin receptor-like receptor (CRLR), Receptor activity-modifying protein 1 (RAMP1), CGRP-receptor component protein (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.