Bruce R. Blazar, Principal Investigator
Angela Panoskaltsis-Mortari, Co-Principal Investigator

Identification of Gene Expression of Type II Pneumocytes

Keratinocyte growth factor (KGF) is a potent mediator of epithelial cell proliferation, as well as a growth factor for type II pneumocytes. KGF has also demonstrated cytoprotective properties against chemotherapy and radiation-induced injury. These researchers have previously shown that KGF administration prior to chemotherapy-induced injury ameliorates graftversus- host disease and idiopathic pneumonia syndrome in a murine allogeneic bone marrow transplantation model. Investigations into the role of KGF in the lung have observed increased lung surfactant levels, increased alveolar fluid clearance, and decreased hyperoxic injury of type II pneumocytes. In order to further evaluate the mechanism of KGF-induced protection of the lung, these researchers are performing microarray analysis on KGF receptor-positive lung cells. To do this, they use laser capture microdissection to collect KGF receptor positive cells from innumohistochemically stained mouse lungs after 24 and 73 hours of systemic KGF administration. Then, ribonucleic acid (RNA) is isolated from the captured cells and amplified through two subsequent rounds of in vitro transcription. The resulting RNA is then applied to an Affymetrix GeneChip for expression analysis.

The researchers hypothesize that they will find increases in expression of genes involved in deoxyribonucleic acid repair, surfactant production, alveolar fluid clearance, and other protective processes. They think they may also see a decrease in expression of apoptotic genes. After characterization of genes important for protection by KGF, the researchers may be able to investigate possible avenues for increasing the therapeutic benefit of KGF treatment.