Connective tissue plays a dynamic role in lung development, growth & healing. In addition to providing structural integrity & a supporting framework for lung cells, components of the lung extracellular matrix (ECM) have various biologic functions in embryogenesis & tissue repair. Proteoglycans are macromolecules which consist of a protein core with one or more glycosaminoglycan (GAG) side chains, & are known to play important roles in cell attachment, spreading & proliferation, cytodifferentiation, matrix assembly, & growth factor/receptor binding in a variety of tissues. The GAG chains comprise approximately 50% of their respective proteoglycan molecules and most studies have concentrated on analyses of these components. It is the core protein however, which appears to confer specificity by directing GAG chain synthesis, targeting the proteoglycans to anatomical sites, & interacting with membrane lipids, proteins & the ECM. Three families of proteoglycans have been described in lung; intracellular, cell surface associated & ECM associated, however little is known about the regulation and expression of these molecules during development & in response to injury in this organ. This project will focus on the ECM associated, fibroblast-derived proteoglycans; decorin & biglycan, which bind the specific growth factor TGF-beta & are thought to play key roles in embryogenesis & healing. We have developed monoclonal antibodies & polymerase chain reaction generated cDNA probes for decorin & biglycan which will be used in experiments designed to achieve the following objectives: l. Determine & localize the developmental expression & regulation of the extracellular matrix associated proteoglycans decorin & biglycan in rat lung. 2. Determine the expression of decorin & biglycan during hyperoxia-induced lung injury & healing.
| Veness-Meehan, Kathleen A; Pierce, Richard A; Moats-Staats, Billie M et al. (2002) Retinoic acid attenuates O2-induced inhibition of lung septation. Am J Physiol Lung Cell Mol Physiol 283:L971-80 |
| Veness-Meehan, K A; Bottone Jr, F G; Stiles, A D (2000) Effects of retinoic acid on airspace development and lung collagen in hyperoxia-exposed newborn rats. Pediatr Res 48:434-44 |
| Veness-Meehan, K A; Moats-Staats, B M; Maniscalco, W M et al. (1997) Changes in decorin expression with hyperoxic injury to developing rat lung. Pediatr Res 41:464-72 |
| Veness-Meehan, K A; Moats-Staats, B M; Price, W A et al. (1997) Re-emergence of a fetal pattern of insulin-like growth factor expression during hyperoxic rat lung injury. Am J Respir Cell Mol Biol 16:538-48 |
