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日本草药半夏泻心汤通过激活细胞外信号调节激酶介导CXCL12的表达来诱导口腔角质形成细胞迁移。

The Japanese Herbal Medicine Hangeshashinto Induces Oral Keratinocyte Migration by Mediating the Expression of CXCL12 Through the Activation of Extracellular Signal-Regulated Kinase.

作者信息

Miyano Kanako, Hasegawa Seiya, Asai Noriho, Uzu Miaki, Yatsuoka Wakako, Ueno Takao, Nonaka Miki, Fujii Hideaki, Uezono Yasuhito

机构信息

Division of Cancer Pathophysiology, National Cancer Research Institute, Tokyo, Japan.

Department of Pain Control Research, The Jikei University School of Medicine, Tokyo, Japan.

出版信息

Front Pharmacol. 2022 Jan 18;12:695039. doi: 10.3389/fphar.2021.695039. eCollection 2021.

DOI:10.3389/fphar.2021.695039
PMID:35145397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8822321/
Abstract

Several clinical studies have reported that Japanese herbal medicine Hangeshashinto (HST) has beneficial effects on chemotherapy-induced oral ulcerative mucositis (OUM). Our previous research demonstrated that HST improves chemotherapy-induced OUM through human oral keratinocyte (HOK) migration, which was suppressed by mitogen-activated protein kinase (MAPK) and C-X-C chemokine receptor 4 (CXCR4) inhibitors. However, the association between these molecules and HOK migration was unclear. Here, we examined the effects of HST on the expression of CXCR4/CXCR7 and C-X-C motif chemokine ligands 11 and 12 (CXCL11/CXCL12) in HOKs. Our results indicated that HST upregulated CXCL12, but not CXCR4, CXCR7, nor CXCL11 in HOKs. HST-induced expression of CXCL12 was significantly suppressed by an inhibitor of extracellular signal-regulated kinase (ERK), but not of p38 and c-Jun N-terminal kinase (JNK). In addition, HST induced phosphorylation of ERK in HOKs. These findings suggest that HST enhances HOK migration by upregulating CXCL12 via ERK.

摘要

多项临床研究报告称,日本草药半夏泻心汤(HST)对化疗引起的口腔溃疡性黏膜炎(OUM)具有有益作用。我们之前的研究表明,HST通过人口腔角质形成细胞(HOK)迁移改善化疗引起的OUM,而丝裂原活化蛋白激酶(MAPK)和C-X-C趋化因子受体4(CXCR4)抑制剂会抑制这种迁移。然而,这些分子与HOK迁移之间的关联尚不清楚。在此,我们研究了HST对HOK中CXCR4/CXCR7以及C-X-C基序趋化因子配体11和12(CXCL11/CXCL12)表达的影响。我们的结果表明,HST上调了HOK中的CXCL12,但未上调CXCR4、CXCR7或CXCL11。细胞外信号调节激酶(ERK)抑制剂可显著抑制HST诱导的CXCL12表达,而p38和c-Jun氨基末端激酶(JNK)抑制剂则无此作用。此外,HST诱导了HOK中ERK的磷酸化。这些发现表明,HST通过ERK上调CXCL12来增强HOK迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/038582a6da8b/fphar-12-695039-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/befe210d85b3/fphar-12-695039-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/8d67c259b17a/fphar-12-695039-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/8af57995ce87/fphar-12-695039-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/895b894ef169/fphar-12-695039-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/f56f407c2653/fphar-12-695039-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/038582a6da8b/fphar-12-695039-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/befe210d85b3/fphar-12-695039-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/8d67c259b17a/fphar-12-695039-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/8af57995ce87/fphar-12-695039-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/895b894ef169/fphar-12-695039-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/f56f407c2653/fphar-12-695039-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c48b/8822321/038582a6da8b/fphar-12-695039-g006.jpg

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