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Am J Physiol Lung Cell Mol Physiol 288: L159-L166, 2005. First published September 24, 2004; doi:10.1152/ajplung.00089.2004
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Alterations in lung mechanics in decorin-deficient mice

Anita Fust,1 Frederique LeBellego,1 Renato V. Iozzo,2 Peter J. Roughley,3 and Mara S. Ludwig1

1Meakins Christie Laboratories and 3Genetics Unit, Shriner's Hospital for Crippled Children, McGill University, Montreal, Quebec, Canada; and 2Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania

Submitted 15 March 2004 ; accepted in final form 14 September 2004

Decorin, a small leucine-rich proteoglycan with a widespread tissue distribution, is required for the normal fibrillogenesis of collagen in most tissues. Because collagen is important in determining the elastic behavior of the lung, we hypothesized that lung tissue mechanics would be altered in a mutant mouse in which the single decorin gene was abrogated by targeted deletion (Dcn–/–). Complex impedance of the respiratory system was measured in C57Bl/6 mice (Dcn–/– and Dcn+/+) using a small animal ventilator that delivers a volume signal with multiple frequencies to the trachea. A constant-phase model was fit to calculate airway resistance (Raw), tissue damping, and tissue elastance. Compliance of the respiratory system (Crs) was measured from a pressure volume curve during stepwise deflations. Lungs were excised, and parenchymal tissue strips were mounted in an organ bath for in vitro measurement of tissue impedance and quasistatic length-stress curves. In addition, pulmonary tissue was examined by immunohistochemistry and immunoblotting. In vivo, in the Dcn–/– mice, Raw was decreased and Crs was increased. Similarly, in vitro, length-stress curves showed increased compliance of the strips in the Dcn–/– mice. These alterations in lung tissue mechanical behavior in Dcn–/– mice support a critical role for decorin in the formation of the lung collagen network.

complex impedance; pressure-volume curves; length-stress curves


Address for reprint requests and other correspondence: M. S. Ludwig, Meakins Christie Laboratories, McGill Univ., 3626 St. Urbain St., Montreal, Quebec, Canada H2X 2P2 (E-mail: mara.ludwig{at}mcgill.ca)




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