HB-EGF Plays a Pivotal Role in Mucosal Hyperplasia During Otitis Media Induced by a Viral Analog.
HB-EGF Plays a Pivotal Role in Mucosal Hyperplasia During Otitis Media Induced by a Viral Analog.
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DOI：
10.3389/fcimb.2022.823714
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发表时间：
2022
影响因子：
5.7
通讯作者：
Kurabi A
中科院分区：
文献类型：
--
作者：
Sakamoto T;Pak K;Chavez E;Ryan AF;Kurabi A
中耳炎（OM）是最常见的儿童疾病，可由细菌和/或病毒感染引起。中耳（ME）粘膜增生是OM的重要组成部分，导致其有害后遗症。我们以前的研究表明，ME粘膜增生细菌诱导OM与肝素结合表皮生长因子（HB-EGF）基因的表达，HB-EGF诱导ME粘膜外植体在文化中的增殖。我们使用单细胞RNA-Seq来鉴定表达Hbegf和参与介导对该因子的反应的相关基因的ME细胞。为了确定病毒感染可能诱导粘膜增生的程度，并评估HB-EGF在体内增生中的作用，我们使用Poly（I：C）模拟ME病毒感染，Western印迹法确认ME蛋白表达，并使用特异性抑制剂阻断HB-EGF在OM期间的作用。HB-EGF及其受体基因在ME中主要由上皮细胞、基质细胞和内皮细胞表达。Poly（I：C）诱导了显著的ME粘膜增生，在ME注射后两天达到峰值。免疫染色显示，裂解成其可溶性形式（sHB-EGF）的proHB-EGF强烈诱导Poly（I：C）。抑制sHB-EGF受体显着减少粘膜的增生反应。结果表明，病毒双链RNA相互作用的合成类似物可以诱导OM，包括ME粘膜的强烈增殖反应，不依赖于细菌。它们还表明，HB-EGF是体内ME粘膜增生的主要生长因子。
Otitis media (OM), the most common childhood illness, can be caused by bacterial and/or viral infection. Hyperplasia of the middle ear (ME) mucosa is an important component of OM that contributes to its deleterious sequelae. Our previous research revealed that ME mucosal hyperplasia in bacterially induced OM was associated with expression of the heparin-binding epidermal growth factor (HB-EGF) gene, and that HB-EGF induced the proliferation of ME mucosal explants in culture. We used single-cell RNA-Seq to identify ME cells that express Hbegf and related genes involved in mediating responses to this factor. To determine the degree to which a viral infection might induce mucosal hyperplasia, and to assess the role of HB-EGF in hyperplasia in vivo, we used, Poly(I:C) to simulate a ME viral infection, Western blotting to confirm ME protein expression, and a specific inhibitor to block the effects of HB-EGF during OM. Genes for HB-EGF and its receptor were expressed in the ME primarily by epithelial, stromal and endothelial cells. Poly(I:C) induced prominent ME mucosal hyperplasia, peaking two days after ME injection. Immunostaining revealed that cleavage of proHB-EGF into its soluble form (sHB-EGF) was strongly induced in response to Poly(I:C). Inhibition of the sHB-EGF receptor dramatically reduced the hyperplastic response of the mucosa. The results demonstrate that a synthetic analog of viral double-stranded RNA interaction can induce OM including a strong proliferative response of the ME mucosa, independent of bacteria. They also indicate that HB-EGF is the dominant growth factor responsible for ME mucosal hyperplasia in vivo.
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影响因子：
10.5
作者：
MCCARTHY, SA;SAMUELS, ML;MCMAHON, M
通讯作者：
MCMAHON, M
影响因子：
5.5
作者：
Kurabi A;Pak K;Ryan AF;Wasserman SI
通讯作者：
Wasserman SI
影响因子：
14.2
作者：
Ebmeyer, J;Furukawa, M;Wasserman, S
通讯作者：
Wasserman, S
影响因子：
3.1
作者：
Melhus, Å;Ryan, AF
通讯作者：
Ryan, AF
DOI：
10.1073/pnas.91.22.10350
发表时间：
1994-10-25
影响因子：
11.1
作者：
BENN, J;SCHNEIDER, RJ
通讯作者：
SCHNEIDER, RJ