PubMed Health⌕ Search

Biomedical subjects

R N Grove

Publications and source records attributed to R N Grove.

7 recordsLinked to original sources
PubMed1995

Adrenal hormone regulation of extracellular matrix synthesis by type II cells.

Previous studies suggested an association between changes in extracellular matrix (ECM) and pulmonary epithelial cell growth and differentiation in lungs of adrenalectomized rats. The role of adrenal hormones to modulate synthesis of cell and ECM proteins by type II epithelial cells was thus investigated. In cells isolated from lungs of adrenalectomized animals, synthesis of ECM proteins was stimulated to a greater extent than was synthesis of cell proteins. This resulted in increased relative synthesis of matrix components. Conversely, dexamethasone (200 nM) treatment in vitro reduced the effects of adrenalectomy and, in control cells, decreased relative ECM synthesis. The magnitude of these effects depended on time in culture and serum conditions. For example, culture of normal cells in serum-free medium mimicked the effects of adrenalectomy, whereas there were no effects of dexamethasone in the presence of serum. These results indicate a role for adrenal steroid hormones to modulate ECM metabolism by type II pulmonary epithelial cells and suggest that consequent effects on ECM biological activity may modify epithelial cell differentiation or growth.

Adrenalectomy↗
PubMed1992

Extracellular matrix synthesis and turnover by type II pulmonary epithelial cells.

Both type I and type II pulmonary epithelial cells contact the extracellular matrix (ECM). Type II cell-ECM interactions are bidirectional; they involve matrix-mediated modulation of type II cell differentiation, as well as cellular synthesis and deposition of ECM components. The present experiments examine the kinetics of accumulation of newly synthesized proteins in cell and matrix fractions from primary cultures of type II pneumocytes. Cycloheximide-sensitive incorporation of [3H]leucine into total protein of both the cell and ECM fractions was linear for 24-30 h, when steady-state labeling was reached and maintained to at least day 8. Over this interval, the cells enlarged but did not divide. Newly synthesized proteins recovered in the matrix fraction averaged 1-2% of those in the cells. Relative rates of radiolabeling of matrix proteins peaked at culture day 2 and increased in the absence of serum. In short-pulse studies, initial rates of protein synthesis were equal on culture days 1 and 3; this suggested that the steady-state labeling kinetics above reflected protein turnover. This was supported by rapid loss of radioactivity from the ECM after fresh type II cells were seeded on a prelabeled, cell-free matrix surface. Fresh or conditioned Dulbecco's modified Eagle's medium containing 10% fetal calf serum had little effect on matrix stability. These results demonstrate regulated deposition and turnover of a complex ECM by type II cells and provide a basis for further investigations of factors that control these processes.

Animals↗
PubMed1989

Matrix-derived soluble components influence type II pneumocytes in primary culture.

Type II pulmonary epithelial cells cultured on a plastic surface fail to retain differentiated form and function. During the first 3 days in primary culture, the cells flatten and lose characteristic lamellar inclusions; they increase in size and exhibit accelerated rates of protein synthesis and thymidine incorporation. These transitions are inhibited markedly if the cells are plated on matrigel (MG), a laminin-rich surface derived from the Englebreth-Holm-Swarm (EHS) sarcoma. Soluble components released from matrigel (MGS) mimic some of the effects of the solid gel. As on a plastic surface, the cells flatten when exposed to MGS during culture. In contrast, MGS inhibits thymidine incorporation and protein synthesis; it is most effective when added early in the culture interval. Direct contact of the cells with the matrigel surface itself is always more effective than maximal MGS activity. The effects of MGS are not reproduced by purified laminin or by transforming growth factor-beta, both of which are present in matrigel. These results indicate that the effects of the solid matrigel surface on cell morphology are caused in part by direct cell-matrix contact but that additional effects, such as decreased DNA synthesis, can be mediated by activity of solubilized gel components. They further provide a model wherein changes in type II cell morphology and function, which typically occur in parallel during primary culture, can be separated experimentally.

Animals↗