Heregulin activation of ErbB2/ErbB3 signaling potentiates the integrity of airway epithelial barrier |
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Authors: | Gon Yasuhiro Matsumoto Ken Terakado Masahiro Sekiyama Akiko Maruoka Shuichiro Takeshita Ikuko Kozu Yutaka Okayama Yoshimichi Ra Chisei Hashimoto Shu |
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Institution: | aDivision of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30–1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173–8610, Japan |
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Abstract: | BackgroundMembers 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).MethodsTwo 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.ResultsHRG 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.ConclusionThese results indicate that HRG activation of ErbB2/ErbB3 heterodimers is essential for regulation of the permeability barrier in AECs. |
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Keywords: | Airway epithelial cell Tight junction EGFR ErbB3 Heregulin |
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