CFTR-deficiency renders mice highly susceptible to cutaneous symptoms during mite infestation
| Autor: | Takashi Sugiyama, Mary Ann Suico, Hirofumi Kai, Takuya Sugahara, Azusa Tomita, Akiko Niibori, Motohiro Takeya, Shota Mizunoe, Yasuaki Hashimoto, Tomoaki Koga, Shogo Shimasaki, Takashi Sato, Bob J. Scholte, Tsuyoshi Shuto |
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| Rok vydání: | 2010 |
| Předmět: |
Keratinocytes
Mite Infestations Cystic Fibrosis Transmembrane Conductance Regulator Pathology and Forensic Medicine Mice Fibrosis Chloride Channels parasitic diseases Glyburide Nerve Growth Factor medicine Neurites Animals Humans Peripheral Nerves RNA Messenger ΔF508 Molecular Biology Sensitization Cells Cultured Skin integumentary system biology Pruritus Cell Biology medicine.disease Cystic fibrosis transmembrane conductance regulator respiratory tract diseases Transepithelial chloride transport medicine.anatomical_structure Nerve growth factor Phenotype Immunology Chloride channel biology.protein Disease Susceptibility Keratinocyte |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 91(4) |
| ISSN: | 1530-0307 |
| Popis: | Pruritus, also known as itch, is a sensation that causes a desire to scratch. Prolonged scratching exacerbates skin lesions in several skin diseases such as atopic dermatitis. Here, we identify the cystic fibrosis transmembrane conductance regulator (CFTR/Cftr), an integral membrane protein that mediates transepithelial chloride transport, as a determinant factor in mice for the susceptibility to several cutaneous symptoms during mite infestation. Mice that endogenously express dysfunctional Cftr (Cftr(ΔF508/ΔF508)) show significant increase of scratching behavior and skin fibrosis after mite exposure. These phenotypes were due to the increased expression of nerve growth factor (NGF) that augments the sensitization of peripheral nerve fibers. Moreover, protein gene product 9.5 (PGP9.5)-positive neurites were abundant in the epidermis of mite-infested Cftr(ΔF508/ΔF508) mice. Furthermore, mite-infested Cftr(+/+) mice orally administered with a chloride channel inhibitor glibenclamide had higher scratching count and increased level of NGF than vehicle-treated mice. Consistently, mite extract-exposed primary and transformed human keratinocytes, treated with CFTR inhibitor, had significantly higher level of NGF mRNA compared with vehicle-treated, mite extract-exposed cells. These results reveal that CFTR in keratinocytes plays a critical role for the regulation of peripheral nerve function and pruritus sensation, and suggest that Cftr(ΔF508/ΔF508) mice may serve as a novel mouse model that represents NGF-dependent generation of pruritus. |
| Databáze: | OpenAIRE |
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