Regulation of Pulmonary Glycogen in Developing Rat Lung

Weaver, Timothy

Abstract

The synthesis and secretion of pulmonary surfactant by the alveolar Type II epithelial cell during the last 20% of gestation is essential for successful postnatal adaptation to air breathing. Surfactant phospholipids are synthesized from substrates arising from pulmonary glycogen degradation which is subject to regulation by developmental and tissue-specific controls in the perinatal period. The precise temporal and spatial regulation of the accumulation and degradation of pulmonary glycogen during lung development is therefore critical for maturation of the surfactant system. The overall objective of this proposal is to characterize the regulation of expression of the major enzymes involved in the anabolism (Project B) and catabolism (Project 4) of pulmonary glycogen during the perinatal period.
The specific aims are directed toward characterization of 1) the temporal expression of glycogen synthase (G.S.), glycogen phosphorylase (G.P.) and phosphorylase kinase (P.K.) in mouse lung during the perinatal period, to determine if these enzymes are regulated at a pre- translational level 2) the spatial expression of G.S., G.P., and P.K. along the proximo-distal axis of developing mouse respiratory epithelium, to determine if expression of these enzymes is locally regulated and 3) the effects of EGF and TGF-beta on the expression of G.S., G.P. and _P.K. in fetal mouse lung explant culture, to determine if expression of these enzymes is modulated by local factors known to modulate the Type II cell phenotype. These studies will provide new and important information regarding the regulation of expression of key enzymes involved in pulmonary glycogen metabolism. The long term goals of this research are to identify the trigger(s) that initiates surfactant synthesis in the perinatal period and thereby facilitate the design of an appropriate pharmacological treatment for premature infants at risk for respiratory distress syndrome.