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Am J Physiol Regul Integr Comp Physiol 293: R784-R792, 2007. First published May 23, 2007; doi:10.1152/ajpregu.00801.2006
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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Changes in versican and chondroitin sulfate proteoglycans during structural development of the lung

Jessica Faggian,1,2,* Amanda J. Fosang,1 Malgorzata Zieba,1,2,* Megan J. Wallace,2 and Stuart B. Hooper2

1Arthritis Research Group, Department of Pediatrics, University of Melbourne, and Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville; and 2Department of Physiology, Monash University, Clayton, Melbourne, Victoria, Australia

Submitted 14 November 2006 ; accepted in final form 16 May 2007

We have examined whether changes in versican levels, or in the sulfation pattern of its chondroitin sulfate (CS) side chains, are associated with the reduction in perialveolar tissue volumes that characterize lung maturation in late-gestation fetal sheep. Lung tissue was collected from fetuses [90–142 days gestational age (GA)] and lambs (2 wk after term birth). The level and distribution of versican and CS glycosaminoglycans (GAG) were determined using immunohistochemistry, whereas fluorophore-assisted carbohydrate electrophoresis was used to determine changes in CS sulfation patterns. Versican was the predominant CS-containing proteoglycan in the lung and decreased from 19.9 ± 2.7 arbitrary units at 90 days GA to 6.0 ± 0.5 arbitrary units at 142 days GA, in close association (P < 0.05) with the reduction in tissue volumes (from 66.0 ± 4.6 to 25.3 ± 1.5% at 142 days); similar reductions occurred for both chondroitin-6-sulfate and chondroitin-4-sulfate CS side chains. Hyaluronic acid levels decreased from 3,168 ± 641 pmol/µg GAG at 90 days GA to 126 ± 9 pmol/µg GAG at 142 days GA, and the predominant sulfated disaccharide changed from {Delta}-di-6S at 90 days GA to {Delta}-di-4S at term. These data indicate that structural development of the lung is closely associated with marked changes in versican levels and the microstructure of CS side chains in perisaccular/alveolar lung tissue.

lung maturation; fetus; versican mRNA; glycosaminoglycans



Address for reprint requests and other correspondence: S. Hooper, Dept. of Physiology, Monash Univ., Clayton, Melbourne, Victoria 3800, Australia (e-mail: stuart.hooper{at}med.monash.edu.au)







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