Role of Vitamin K in Lung; Lung Development

Our research interests aim to define the physiological regulation and functional significance of vitamin K-dependent g-carboxylation of protein substrates by rat lung and alveolar type II cells. Functional differences in the lung carboxylase enzyme are being compared with the well-known hepatic system, where several of the clotting factors are carboxylated at specific glutamic acid residues. This research will define microsomal carboxylase activity and substrate specificity in freshly isolated type II epithelial cells from normal, hormonally and nutritionally manipulated adult rats. The role of type II cell differentiation in modulating g-carboxylase activity and substrate specificity will be determined during primary culture where differentiated morphology and function can be modified by both laminin- and fibronectin-rich extracellular matrices. Current research has identified one protein named matrix Gla protein (MGP) in type II cells. MGP mRNA and protein are induced during culture and can be regulated by vitamin K status and the extracellular matrix. The identification of additional substrates will lead to a better understanding of both type II and type I cell function as several carboxylated proteins are expressed only after type II cells change to a type I cell-like phenotype in primary culture.