Fetal Lung Fibroblasts Selectively Down-regulate Proteoglycan Synthesis in Response to Elevated Oxygen (*)
- From the Medical Research Council Group in Lung Development, Department of Paediatrics, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario M5G 1X8, Canada
- ¶ To whom correspondence should be addressed: Division of Neonatology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. Tel.: 416-813-6772, Fax: 416-813-5002, mppm{at}resunix.ri.sickkids.on.ca.
Abstract
Cell proliferation is in part regulated by extracellular matrix. Therefore, it is possible that elevated O
may indirectly affect lung fibroblast growth via modulation of extracellular matrix. In the present study, we investigated
the effect of elevated O
on the synthesis of glycosaminoglycans (GAGs) and proteoglycans (PGs) by fetal lung fibroblasts. A 48-h exposure to ≥50%
O
reduced the incorporation of [3H]glucosamine and 
SO
into GAGs by fetal lung fibroblasts. The relative proportion of the individual GAG molecules was not altered by elevated
O
. Fibroblasts exposed to 50% O
secreted less [
S]proteoglycans into the medium than controls. Specifically, the synthesis of the small soluble PG, biglycan, was decreased
by exposure to 50% O
. Fetal lung fibroblasts did not synthesize the small chondroitin/dermatan sulfate PG, decorin. Elevated O
concentrations also reduced the synthesis of membrane- and matrix-associated PGs. Furthermore, exposure of fetal lung fibroblasts
to ≥50% O
resulted in a decreased mRNA expression for biglycan and versican core protein sequences. In contrast, elevated O
increased the message for type I collagen and fibronectin without affecting that of β-actin. The inhibitory effect of elevated
O
on biglycan mRNA and protein expression was overcome by incubating the cells in 3% O
after the 48-h exposure to 50% O
. The latter treatment also reversed the increased mRNA expression of type I collagen associated with elevated O
but not that of fibronectin. These results demonstrate that fetal lung fibroblasts, in response to elevated oxygen concentrations,
selectively down-regulate their GAG and PG synthesis and that this O
effect is reversible.
Footnotes
-
↵§ Recipient of a research fellowship from the Italian Ministry of Education.
-
↵* These studies were supported by a Group grant from the Medical Research Council of Canada and an equipment grant from the Ontario Thoracic Society. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- GAG
-
glycosaminoglycan
- PG
-
proteoglycan
- TGF
-
transforming growth factor
- kb
-
kilobase(s)
- HPLC
-
high performance liquid chromatography
- HBSS (-)
-
Hanks' buffered salt solution without calcium or magnesium
- MEM
-
minimal essential medium
- PBS
-
phosphate-buffered saline.
-
↵2 J. Xu and M. Post, unpublished observation.
-
- Received September 22, 1995.
- Revision received December 18, 1995.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
