This Article Full Text Full Text (PDF) All Versions of this Article: 2007-0377OCv1 40/2/168    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Choi, H. J. Articles by Yoon, J.-H. Search for Related Content PubMed PubMed Citation Articles by Choi, H. J. Articles by Yoon, J.-H.

Signal Pathway of 17β-Estradiol–Induced MUC5B Expression in Human Airway Epithelial Cells

¹ Department of Otorhinolaryngology, ² The Airway Mucus Institute, ³ BK21 Project for Medical Science, ⁴ Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea; ⁵ Department of Otolaryngology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea; ⁶ Department of Otolaryngology–Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea; ⁷ The Unite INSERM 560, Place de Verdun, Lille, France; and ⁸ Department of Pathobiology, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee

Correspondence and requests for reprints should be addressed to Joo-Heon Yoon, M.D., Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea 120-752. E-mail: jhyoon{at}yuhs.ac

MUC5B is a major mucin of the human respiratory tract, and it is not clear how MUC5B expression is regulated in various airway diseases. The goal of this study was to determine the mechanisms by which 17β-estradiol induces MUC5B gene expression in airway epithelial cells. It was found that E2, a sex hormone, stimulates MUC5B gene overexpression by interaction with estrogen receptor (ER) and by acting through extracellular signal–regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK). Pretreatment with ER antagonist ICI 182,780 blocked both E2-induced ERK1/2-MAPK activation and MUC5B gene expression. It was also found that the activation of p90 ribosomal S 6 protein kinase 1 (RSK1), cAMP-response element-binding protein (CREB), and cAMP-response element (CRE) (–956 region of the MUC5B promoter)-responsive signaling cascades via ERK1/2 MAPK are crucial aspects of the intracellular mechanisms that mediate MUC5B gene expression. Taken together, these studies give additional insights into the molecular mechanism of hormone-induced MUC5B gene expression and enhance our understanding of abnormal mucin secretion in response to hormonal imbalances.

Key Words: MUC5B • estrogen • ER • CREB

CLINICAL RELEVANCE These studies give additional insights into the molecular mechanism of hormone-induced MUC5B gene expression and enhance our understanding of abnormal mucin secretion in response to hormonal imbalances.

 

This article has been cited by other articles:

				A. I. Malik and K. B. Storey Activation of extracellular signal-regulated kinases during dehydration in the African clawed frog, Xenopus laevis J. Exp. Biol., August 15, 2009; 212(16): 2595 - 2603. [Abstract] [Full Text] [PDF]