Keratinocyte growth factor stimulates CLC-2 expression in primary fetal rat distal lung epithelial cells

Carol J. Blaisdell, Jason P. Pellettieri, Ceila E. Loughlin, Shijian Chu, Pamela L. Zeitlin

Research output: Contribution to journalArticlepeer-review

Abstract

Keratinocyte growth factor (KGF) is mitogenic for epithelial cells and induces cystic dilation of fetal lung explants through cystic fibrosis transmembrane conductance regulator-independent chloride channels. One candidate fetal lung chloride channel that is highly expressed on the apical surface of the respiratory epithelium and markedly downregulated after birth is CLC-2. We hypothesized that KGF regulates CLC-2 expression in the fetal lung. Primary fetal rat distal lung epithelial cell monolayers were grown in medium containing 10 ng/ml KGF for 48 h. CLC-2 protein was increased by Western blot analysis of whole-cell lysates in KGF-treated cultures. Similarly, KGF stimulated CLC-2 messenger RNA (mRNA) by Northern blot analysis. This enhanced expression was dose-dependent and maximal at 48 h with 10 ng/ml KGF. Promoter-reporter gene experiments demonstrated that KGF did not stimulate gene transcription. By inhibition of new mRNA synthesis with actinomycin D, evidence was obtained that KGF stabilizes CLC-2 mRNA. We speculate that KGF may positively influence pulmonary chloride and fluid secretion by a secondary pathway affecting CLC-2 degradation.

Original languageEnglish (US)
Pages (from-to)842-847
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume20
Issue number4
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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