Heregulin activation of ErbB2/ErbB3 signaling potentiates the integrity of airway epithelial barrier

被引：16

作者：

Gon, Yasuhiro ^{[1
]}

Matsumoto, Ken ^{[1
]}

Terakado, Masahiro ^{[1
]}

Sekiyama, Akiko ^{[1
]}

Maruoka, Shuichiro ^{[1
]}

Takeshita, Ikuko ^{[1
]}

Kozu, Yutaka ^{[1
]}

Okayama, Yoshimichi ^{[1
]}

Ra, Chisei ^{[1
]}

Hashimoto, Shu ^{[1
]}

机构：

[1] Nihon Univ, Sch Med, Dept Internal Med, Div Resp Med,Itabashi Ku, Tokyo 1738610, Japan

来源：

EXPERIMENTAL CELL RESEARCH | 2011年 / 317卷 / 13期

关键词：

Airway epithelial cell; Tight junction; EGFR; ErbB3; Heregulin; GROWTH-FACTOR RECEPTOR; ERBB RECEPTORS; PERMEABILITY; EXPRESSION; LIGANDS; CULTURE; FAMILY; CELLS; HETERODIMERIZATION; DIFFERENTIATION;

D O I：

10.1016/j.yexcr.2011.05.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1947 / 1953

页数：7

共 31 条

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