Effect of a proline analogue, azetidine-2-carboxylic acid, on the morphogenesis <i>in vitro</i> of mouse embryonic lung

Abstract

ABSTRACT A proline analogue, azetidine-2-carboxylic acid, which has been reported to selectively depress collagen biosynthesis, affects lung morphogenesis in vitro by determining differential modifications of the rate of epithelial growth and ramification activity. Low concentrations of the analogue induce a sharp decline of the number of newly formed terminal buds, leaving the rate of global growth of the epithelial tree almost unaffected. This effect is reversed by increasing doses which appear more effective on global epithelial growth than on budding. DNA and protein content at the end of the treatment are unequally reduced. Protein concentration is more depressed with consequent rise of the DNA/protein ratio. These results show that epithelial budding is very sensitive to the treatment with the analogue, and draw attention to collagen biosynthesis as one of the possible mechanisms by which the mesenchyme controls the spatial organization of the epithelial tree. This type of control appears relatively independent on the actual rate of epithelial cell replication, since budding is much more sensitive to the action of the drug.