title: AMPK induces MUC5B expression via p38 MAPK in NCI-H292 airway epithelial cells.
abstract: Adenosine monophosphate-activated protein kinase (AMPK) is a well-known serine/threonine kinase that has been implicated in modulation of glucose and fatty acid metabolism. Recent reports have also implicated AMPK in modulation of mucin secretion. In this study, the effects and signaling pathways of AMPK on MUC5B expression were investigated in human NCI-H292 airway epithelial cells. Metformin, as an activator of AMPK, induced MUC5B expression in a dose-dependent manner. Compound C, as an inhibitor of AMPK, inhibited metformin-induced MUC5B expression in a dose-dependent manner. Metformin significantly activated phosphorylation of AMPK; compound C inhibited metformin-activated phosphorylation of AMPK. Without treatment with metformin, there was no difference in MUC5B mRNA expression between Ad-dnAMPK transfected and wild-type adenovirus transfected NCI-H292 cells. However, after treatment with metformin, MUC5B mRNA expression was increased in wild-type adenovirus transfected NCI-H292 cells; MUC5B mRNA expression was significantly decreased in Ad-dnAMPK transfected NCI-H292 cells. Metformin activated phosphorylation of p38 mitogen-activated protein kinase (MAPK); compound C inhibited metformin-activated phosphorylation of p38 MAPK. SB203580, as an inhibitor of p38 MAPK, significantly inhibited metformin-induced MUC5B mRNA expression, while U0126, as an inhibitor of ERK1/2 MAPK, had no effect. In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked metformin-induced MUC5B mRNA expression. In conclusion, results of this study show that AMPK induces MUC5B expression through the p38 MAPK signaling pathway in airway epithelial cells.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.forename: Jun Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Sang Baik
authors.initials: SB
authors.lastname: Ye
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Kim
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D008687:Metformin / Q000494:pharmacology; D055257:Mucin-5B / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000201:enzymology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B; D008687:Metformin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases