Heregulin activation of ErbB2/ErbB3 signaling potentiates the integrity of airway epithelial barrier
Heregulin activation of ErbB2/ErbB3 signaling potentiates the integrity of airway epithelial barrier
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DOI：
10.1016/j.yexcr.2011.05.010
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发表时间：
2011-08-01
影响因子：
3.7
通讯作者：
Hashimoto, Shu
中科院分区：
文献类型：
--
作者：
Gon, Yasuhiro;Matsumoto, Ken;Hashimoto, Shu
背景：受体蛋白酪氨酸激酶超家族的ErbB家族成员介导调蛋白（HRG）诱导的细胞反应。在这里，我们研究了HRG对ErbB受体的激活，以及这种激活在气道上皮细胞（AEC）中渗透性屏障发展中的作用。两种气道上皮样细胞系，将Calu-3和16 HBE暴露于HRG或无刺激，并通过跨上皮电阻（TER）和异硫氰酸荧光素（FITC）-葡聚糖通量测定其细胞旁通透性进行评价。结果：HRG促进Calu-3和16 HBE细胞单层通透性屏障的形成和紧密连接的形成。Calu-3细胞表面表达ErbB 1、ErbB 2和ErbB 3，但不表达ErbB 4。通过小干扰RNA（siRNA）敲低ErbB 3可减弱HRG对通透性屏障的影响。ErbB 3是一种激酶死亡受体，依赖于该家族的其他成员进行磷酸化。为了鉴定其异源二聚化伴侣，我们敲低了其他ErbB家族受体的表达。结论：HRG激活ErbB 2/ErbB 3异源二聚体是调节AECs通透性屏障的关键。(C)2011 Elsevier Inc. All rights reserved.
Background: Members of the ErbB family of the receptor protein tyrosine kinase superfamily mediate heregulin (HRG)-induced cell responses. Here we investigated HRG activation of ErbB receptors, and the role of this activation in the development of the permeability barrier in airway epithelial cells (AECs).Methods: Two airway epithelial-like cell lines, Calu-3 and 16HBE were exposed to HRG or no stimulus and were evaluated with respect to their paracellular permeability as determined by transepithelial electric resistance (TER) and fluorescein isothiocyanate (FITC)-dextran flux. Tight junctions (TJs) were assessed by immunocytochemical localization of occludin and zonula occludens-1.Results: HRG promoted the development of the permeability barrier and TJ formation by monolayers of Calu-3 and 16HBE cells. Calu-3 cells expressed ErbB1, ErbB2, and ErbB3, but not ErbB4, on their surface. ErbB3 knockdown by small interference RNA (siRNA) blunted the effects of HRG on the permeability barrier. ErbB3 is known as a kinase-dead receptor and relies on other members of the family for its phosphorylation. To identify its heterodimerization partner, we knocked down the expression of other ErbB family receptors. We found that HRG's effect on the permeability barrier could be significantly attenuated by transfecting cells with ErbB2 siRNA but not with EGFR siRNA.Conclusion: These results indicate that HRG activation of ErbB2/ErbB3 heterodimers is essential for regulation of the permeability barrier in AECs. (C) 2011 Elsevier Inc. All rights reserved.