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Am J Physiol Lung Cell Mol Physiol 285: L344-L353, 2003. First published April 4, 2003; doi:10.1152/ajplung.00281.2002
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Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats

Jyoji Yoshizawa,1,3 Cheryl J. Chapin,1 Lourenço Sbragia,1,3 Robert Ertsey,1 Jorge A. Gutierrez,1,2 Craig T. Albanese,1,3 and Joseph A. Kitterman1,2

1Cardiovascular Research Institute, and Departments of 2Pediatrics and 3Surgery, University of California, San Francisco, California 94118

Submitted 15 August 2002 ; accepted in final form 31 March 2003

Fetal tracheal occlusion (TO) has been reported to stimulate lung growth but decreases number and maturation of type II cells, effects that vary with gestational age and duration of TO. We examined effects of a novel method of TO (unipolar microcautery to seal the trachea) produced at 19.5–20 days (d) of gestation in fetal rats; fetuses were delivered at term, 22 d. Controls were sham operated and unoperated littermates. TO increased wet lung weight but not dry lung weight or lung DNA and protein. To evaluate further the effects of TO, we examined the cell cycle regulators, cyclins D1 and A, in fetal lungs. Cyclin D1 increased with TO (P < 0.005). TO also increased expression of the type I epithelial cell marker RTI40 (mRNA and protein). TO decreased mRNA for surfactant proteins (SP)-A and -C but did not affect protein levels of SP-A and -B and of RTII70, a type II epithelial cell marker. We conclude that TO by microcautery, even of short duration, has diverse pulmonary effects including stimulating increased levels of cyclin D1 with probable cell cycle progression, type I cell differentiation, and possibly inhibiting type II cell function.

cyclins; fetal lung development; lung growth; pulmonary epithelial differentiation; pulmonary surfactant


Address for reprint requests and other correspondence: C. J. Chapin, Univ. of California, San Francisco, Cardiovascular Research Institute, Box 1245, 3333 California St., Ste. 150, San Francisco, CA 94118 (E-mail: cheri{at}itsa.ucsf.edu).




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C. J. Chapin, R. Ertsey, J. Yoshizawa, A. Hara, L. Sbragia, J. J. Greer, and J. A. Kitterman
Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation
Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L44 - L52.
[Abstract] [Full Text] [PDF]


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