Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression

Kathryn Holmes, Russell Hales, Shijian Chu, Micah J. Maxwell, Peter J. Mogayzel, Pamela L. Zeitlin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

ClC-2 is a pH- and voltage-activated chloride channel, which is highly expressed in fetal airways and downregulated at birth. The ClC-2 promoter contains consensus binding sites within the first 237 bp, which bind transcription factors Sp1 and Sp3(1). This study directly links Sp1 and Sp3 with ClC-2 protein expression by demonstrating: (i) induction of ClC-2 protein by transient overexpression of each transcription factor in adult rat Type II cells, which have low levels of ClC-2; and (ii) reduction of ClC-2 expression by incubation with a competitive inhibitor of Sp1 and Sp3 in fetal rat Type II cells, which have high levels of endogenous ClC-2. Endogenous fetal lung Sp1 is differentially expressed as two major species of 105 kD and 95 kD. Although low-level expression of Sp1 in adult cells is almost exclusively the 105-kD species, overexpression of Sp1 results in increased expression of the 95-kD band. These experiments suggest that the mechanism for postnatal reduction of ClC-2 expression in lung epithelia is based on decreased interaction of Sp1 and Sp3 with the ClC-2 promoter.

Original languageEnglish (US)
Pages (from-to)499-505
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume29
Issue number4
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

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Rats
Sp3 Transcription Factor
Epithelial Cells
Modulation
Sp1 Transcription Factor
Lung
Chloride Channels
Proteins
Transcription Factors
Binding Sites
Electric potential
Down-Regulation
Epithelium
Parturition
Experiments
ClC-2 chloride channels

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression. / Holmes, Kathryn; Hales, Russell; Chu, Shijian; Maxwell, Micah J.; Mogayzel, Peter J.; Zeitlin, Pamela L.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 4, 01.10.2003, p. 499-505.

Research output: Contribution to journalArticle

Holmes, Kathryn ; Hales, Russell ; Chu, Shijian ; Maxwell, Micah J. ; Mogayzel, Peter J. ; Zeitlin, Pamela L. / Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression. In: American Journal of Respiratory Cell and Molecular Biology. 2003 ; Vol. 29, No. 4. pp. 499-505.
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