Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates

Y. Chen, Hua Zhao Yu Hua Zhao, Reen Wu

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5′-triphosphate (UTP) ≈ adenosine 5′-triphosphate (ATP) ≈ ATP-γ-S > uridine 5′-diphosphate ≈ adenosine 5′-diphosphate > α,β-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.

Original languageEnglish (US)
Pages (from-to)409-417
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume25
Issue number4
StatePublished - 2001

Fingerprint

Uridine Triphosphate
Mucins
Gene expression
Nucleotides
Uridine
Gene Expression
Adenosine Triphosphate
Pertussis Toxin
Adenosine
Mitogen-Activated Protein Kinases
GTP-Binding Proteins
Epithelial Cells
Pyrimidine Nucleotides
Type C Phospholipases
Protein C
triphosphoric acid
Sodium Chloride
Adenosine Diphosphate
Protein Kinase C
Epithelium

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates. / Chen, Y.; Yu Hua Zhao, Hua Zhao; Wu, Reen.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 25, No. 4, 2001, p. 409-417.

Research output: Contribution to journalArticle

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