Signal pathway of 17beta-estradiol-induced MUC5B expression in human airway epithelial cells.
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 17beta-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 alpha (ERalpha) 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.
Choi
Hye Joung
HJ
Department of Otorhinolaryngology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea.
Chung
Yoo-Sam
YS
Kim
Hyun Jik
HJ
Moon
Uk Yeol
UY
Choi
Yeon Ho
YH
Van Seuningen
Isabelle
I
Baek
Seung Joon
SJ
Yoon
Ho-Geun
HG
Yoon
Joo-Heon
JH
D000328:Adult; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D055257:Mucin-5B / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; C524578:MUC5B protein, human; D055257:Mucin-5B; D000077267:Fulvestrant; D004958:Estradiol; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3