Hepcidin expression in the trigeminal ganglion and the oral mucosa in an oral ulcerative mucositis rat model.
Hepcidin expression in the trigeminal ganglion and the oral mucosa in an oral ulcerative mucositis rat model.
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DOI：
10.1371/journal.pone.0284617
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Ono, Kentaro
中科院分区：
文献类型：
--
作者：
Hitomi, Suzuro;Nodai, Tomotaka;Kokabu, Shoichiro;Shikayama, Takemi;Sago-Ito, Misa;Nakatomi, Chihiro;Terawaki, Kiyoshi;Omiya, Yuji;Shinoda, Masamichi;Ono, Kentaro
严重的口内疼痛会导致进食和说话困难，导致生活质量下降。然而，口腔内疼痛的分子机制尚不清楚。在此，我们研究了醋酸诱导的口腔溃疡性粘膜炎大鼠模型中三叉神经节的基因调控和口内疼痛相关行为。醋酸作用于雄性Wistar大鼠口腔黏膜后第2天出现口腔溃疡，引起自发性疼痛和机械异常性疼痛。三叉神经节组织的脱氧核糖核酸芯片分析表明，Hamp（一种调节细胞铁转运的hepcidin基因）是上调最多的基因。在口腔溃疡性粘膜炎模型中，Hamp在溃疡区也有表达上调，但在肝脏中没有表达上调，血浆和唾液中hepcidin水平未升高，说明模型中hepcidin是在溃疡区局部产生的。全身抗生素预处理未增加三叉神经节和溃疡区Hamp mRNA水平。口腔黏膜注射Hepcidin可增强三叉神经内插亚核/尾侧神经元对口腔黏膜有害机械刺激的兴奋性。这些结果提示口腔溃疡性黏膜炎由于溃疡区感染性炎症引起口腔黏膜疼痛，增强了Hamp， Hamp代表溃疡区和三叉神经节中抗菌和抗肽酶基因的表达。hepcidin调节细胞铁运输可能参与口腔溃疡性粘膜炎引起的疼痛。
Severe intraoral pain induces difficulty in eating and speaking, leading to a decline in the quality of life. However, the molecular mechanisms underlying intraoral pain remain unclear. Here, we investigated gene modulation in the trigeminal ganglion and intraoral pain-related behavior in a rat model of acetic acid-induced oral ulcerative mucositis. Oral ulceration was observed on day 2 after acetic acid treatment to the oral mucosa of male Wistar rats, causing spontaneous pain and mechanical allodynia. Deoxyribonucleic acid microarray analysis of trigeminal ganglion tissue indicated that Hamp (a hepcidin gene that regulates cellular iron transport) was the most upregulated gene. In the oral ulcerative mucositis model, the upregulation of Hamp was also induced in the ulcer region but not in the liver, with no increase in hepcidin levels in the plasma and saliva, indicating that hepcidin was produced locally in the ulcer region in the model. Systemic antibiotic pretreatment did not increase the mRNA levels of Hamp in the trigeminal ganglion and ulcer regions. Hepcidin injection into the oral mucosa enhanced neuronal excitability in response to noxious mechanical stimulation of the oral mucosa in trigeminal spinal subnucleus interpolaris/caudalis neurons. These results imply that oral ulcerative mucositis induces oral mucosal pain because of infectious inflammation of the ulcerative area and potentiates Hamp, which represents anti-bacterial and anti-peptidase gene expression in the ulcer region and trigeminal ganglion. The regulation of cellular iron transport by hepcidin is likely involved in oral ulcerative mucositis-induced pain.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
4.4
作者：
Hirano T
通讯作者：
Hirano T
影响因子：
7.4
作者：
Barclay, Jane;Clark, Anna K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia
影响因子：
3.1
作者：
Kim HY;Lee I;Chun SW;Kim HK
通讯作者：
Kim HK
影响因子：
1.9
作者：
Lima, V;Brito, GAC;Ribeiro, RA
通讯作者：
Ribeiro, RA