Abnormalities of lung growth, such as pulmonary hypoplasia and lung bud anomalies, are important causes of morbidity and mortality in the newborn period and later life. Postnatal lung growth and regeneration of damaged lung tissue are important for continued normal pulmonary function in later life as well. The regulation of the normal and abnormal lung growth precess at a cellular level is not well understood. The objective of this project is to examine role of growth factors, specifically somatomedin C/insulinlike growth factor I (SmC) and fibroblast pneumonocyte growth factor (FPGF) during these processes. Initially, the ontogeny of SmC production by fetal and adult lungs will be determined using tissue extraction and radioimmunoassay for SmC of the extracts. Tissue from lungs in altered growth states, pulmonary hypoplasia and regenerating lungs, will then be studied using the same techniques. The production of SmC by primary cultures of fetal alveolar type II cells and lung fibroblasts will be examined using radioactive amino acid labelling of secreted proteins, affinity chromatography with SmC antibodies coupled to sepharose and HPLC purification of the antibody bound radio-labelled proteins. The expression of specific mRNA for SmC will be determined for these lung cells using Northern hybridization with a specific rat SmC cDNA probe. FPGF, a paracrine growth factor which is elaborated by fetal lung fibroblasts and stimulates the growth of the fetal alveolar type II cell, will be purified. A bioassay of fetal type II cell (H3) thymidine incorporation will be used to follow this process. Polyclonal antibodies to FPGF will be raised and a radioimmunoassay developed for FPGF. FPGF will also be used to study the biological effects of FPGF in vitro and in vivo. Finally, regulation of FPGF production in normal and altered lung growth states and in vitro will be studied using the RIA and bioassay.
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