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To assess the temporal and spatial expression of the matrix-associated proteoglycan, biglycan, in a model of chronic hyperoxia-induced lung injury, changes in mRNA and protein were examined using Northern blot analyses and immunohistochemistry. Newborn rats were exposed to 85% or 100% oxygen for 6 and 4 wk, respectively. Exposure to 85% oxygen for up to 6 wk resulted in a reduction in lung surface area and the development of focal areas of fibrosis. In contrast, exposure to 100% oxygen resulted in gross alterations in lung histology with greatly enlarged airspaces and septal thickening. Biglycan mRNA increased at 3 to 5 wk in control animals, then returned to baseline, while oxygen-exposed animals showed a further increase after 2 to 4 wk of exposure. Immunoreactive biglycan decreased with postnatal age but increased in alveolar cells of animals exposed to 100% oxygen for 4 wk and in alveolar cells and along alveolar septae of animals exposed to 85% oxygen for 6 wk. We speculate that biglycan binds growth factors such as transforming growth factor-beta near these cells, acting in an autoregulatory fashion to support epithelial cell proliferation and inhibit mesenchymal cell proliferation.