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Synthesis and deposition of proteoglycans in fibroproliferative lung disease Burke, Adrian Kevin


Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation leading to progressive deposition of collagenous extracellular matrix. Proteoglycan metabolism may be altered in inflammation and fibrosis. The aim of this study is to characterize changes in proteoglycan synthesis and deposition in the remodeling lung. Lung biopsy tissue from 6 IPF and 6 control patients was studied using histochemistry and immunohistochemistry. Histochemistry revealed dense deposits of glycosaminoglycan in fibroblast foci unique to remodeling lung, which enzyme digestion showed to contain predominantly chondroitin sulfate/dermatan sulfate. Immunohistochemistry showed that glycosaminoglycan deposition was concordant with versican, but not decorin, biglycan or hyaluronan. The distribution of versican, decorin, biglycan and hyaluronan were described in the normal and IPF lung for the first time. Versican in IPF was associated with a-smooth muscle actin (α-SMA)-positive myofibroblasts migrating into airspace and myofibroblasts in fibroblast foci. In control and diseased lung, versican was associated with smooth muscle in blood vessel walls, in airway walls and with α -SMA-positive cells in alveolar entrance rings. 22.6%±4.1% of tissue area in IPF biopsies was versican-positive, compared to 2.6±2.0% of tissue area in control lung (p

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