Journal of Biological Chemistry
Volume 274, Issue 35, 27 August 1999, Pages 25167-25172
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CELL BIOLOGY AND METABOLISM
Elastase-mediated Release of Heparan Sulfate Proteoglycans from Pulmonary Fibroblast Cultures: A MECHANISM FOR BASIC FIBROBLAST GROWTH FACTOR (bFGF) RELEASE AND ATTENUATION OF bFGF BINDING FOLLOWING ELASTASE-INDUCED INJURY*

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We have investigated elastase-mediated alterations in the expression of basic fibroblast growth factor (bFGF) receptors and proteoglycan co-receptors and characterized the subsequent effects on bFGF receptor binding profiles. For these studies, pulmonary fibroblast cultures were treated with porcine pancreatic elastase, and elastase-mediated changes in bFGF receptor expression and binding profiles were assessed. Quantitation of [35S]sulfate-labeled proteoglycan and total glycosaminoglycan release from fibroblast matrices indicated that elastase treatment released sulfated proteoglycan from the cell surface in a time- and dose-dependent fashion that correlated strongly with elastase-mediated bFGF release. Ligand binding studies indicated that elastase treatment decreased total binding of125I-bFGF to the cell surface and affected both fibroblast growth factor receptor and heparan sulfate proteoglycan (HSPG) binding sites. Western blot analyses indicated that elastase treatment did not release significant amounts of fibroblast growth factor receptor protein. These findings indicate that elastase-mediated HSPG release from fibroblast matrices reduces the effective affinity of bFGF for its receptor. Collectively, these studies suggest that HSPG co-receptors are important mediators of the pulmonary fibroblast response to elastase treatment and that bFGF, HSPG, and other elastase-released entities play an important role in the response of the lung to chronic injury.

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This work was supported by National Institutes of Health Grant PO1HL46902.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.