title: Src homology 2-containing protein tyrosine phosphatase-2 acts as a negative regulator for MUC5AC transcription via the inhibition of the ERK1/2 MAPK signalling pathway in the airway.
abstract: OBJECTIVE
  Mucus hypersecretion has been frequently observed in inflammation respiratory diseases. However, the negative regulators for mucus overproduction have not been readily identified. Our work focused on identifying novel negative regulator that modulates mucus overproduction in the human respiratory system. Herein, we examined whether H2 O2 could induce MUC5AC transcription in a dose-dependent manner and activate tyrosine phosphatase (SHP)-2 in human airway epithelial cells.
  
  
  METHODS
  We performed qRT-PCR to detect the changes in MUC5AC transcription and dot-blotting analysis to investigate MUC5AC secretion as regulated by SHP-2.
  
  
  RESULTS
  H2 O2 induced MUC5AC transcription in a dose-dependent manner and dramatically activated SHP-2. In addition, whereas wild-type SHP-2 completely inhibited H2 O2 -induced MUC5AC transcription, siRNA-SHP-2 restored it interestingly, suggesting that SHP-2 may act as a negative regulator for mucus overproduction and hypersecretion in the human respiratory tract. Moreover, SHP-2 inhibited the ERK1/2 MAPK pathway, thus abolishing the signalling for MUC5AC transcription.
  
  
  CONCLUSIONS
  We found that H2 O2 induced SHP-2 activation, which acted as a suppressor in H2 O2 signalling to regulate MUC5AC transcription in the airway.
authors.affiliation: Department of Physiology, Kosin University College of Medicine, Busan 602-703, Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Song
authors.forename: J K
authors.initials: JK
authors.lastname: Choi
authors.forename: D W
authors.initials: DW
authors.lastname: Ahn
mesh_terms: D018277:Carcinoma, Mucoepidermoid; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D055785:Gene Knockdown Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008175:Lung Neoplasms; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D055271:Mucin 5AC / Q000235:genetics* / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016877:Oxidants; D006861:Hydrogen Peroxide; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11