Submitted on November 14, 2006
Accepted on May 16, 2007
Changes in versican and chondroitin sulphate proteoglycans during structural development of the lung
Jessica Faggian1, Amanda J Fosang2, Malgorzata Zieba3, Megan J Wallace4, and Stuart Brian Hooper5*
1 Pediatrics, University of Melbourne, Melbourne, Victoria, Australia; Arthritis Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia; Physiology, Monash University, Monash University, Australia
2 Pediatrics, University of Melbourne, Melbourne, Victoria, Australia; Arthritis Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
3 Physiology, Monash University, Melbourne, Victoria, Australia
4 Physiology, Monash University, Monash University, Australia
5 Physiology, Monash University, Monash University, Victoria, Australia
* To whom correspondence should be addressed. E-mail: stuart.hooper{at}med.monash.edu.au.
We have examined whether changes in versican levels, or in the sulphation pattern of its chondroitin sulphate (CS) side chains, are associated with the reduction in peri-alveolar tissue volumes that characterise lung maturation in late gestation fetal sheep. Lung tissue was collected from fetuses (90-142 days GA) and lambs (2 weeks after term birth). The level and distribution of versican and CS glycosaminoglycans (GAG) was determined using immunohistochemistry whereas fluorophore assisted carbohydrate electrophoresis (FACE) was used to determine changes in CS sulphation patterns. Versican was the predominant CS-containing proteoglycan in the lung and decreased from 19.9±2.7 arbitrary units (au) at 90d GA to 6.0±0.5 au at 142d GA in close association (p<0.05) with the reduction in tissue volumes (from 66.0±4.6% to 25.3±1.5% at 142d); similar reductions occurred for both C-6-S and C-4-S CS side chains. Hyaluronic acid (HA) levels decreased from 1397±258.8 pmol/µg GAG at 90d GA to 92.9±9.9 pmol/µg GAG at 142d GA and the predominant sulfated disaccharide changed from 
-di-6S at 90d GA to -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 peri-saccular/alveolar lung tissue.
