Published ahead of print on April 24, 2003, doi:10.1165/rcmb.2003-0030OC Am. J. Respir. Cell Mol. Biol., Volume 29, Number 4, October 2003, 499-505 A more recent version of this article appeared on October 1, 2003
Submitted on January 28, 2003 Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expressionKathryn W Holmes1,1 Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, MD, USA, 2 McGuire Research Institute, Richmond, VA, USA * To whom correspondence should be addressed. E-mail: pzeitlin{at}jhmi.edu.
ClC-2 is a pH- and voltage-activated chloride channel, which is highly expressed in fetal airways and down-regulated at birth. The ClC-2 promoter contains consensus binding sites within the first 237 bp, which bind transcription factors Sp1 and Sp3(9). This study directly links Sp1 and Sp3 with ClC-2 protein expression by demonstrating: 1) induction of ClC-2 protein by transient over-expression of each transcription factor in adult rat Type II cells which have low levels of ClC-2; and 2) 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. While 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 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.
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