SPARC PARTICIPATES IN THE BRANCHING MORPHOGENESIS OF DEVELOPING FETAL-RAT LUNG

Adhesion of cells to components of the extracellular matrix has been s hown to be critical in normal lung development, particularly during th e pseudoglandular stage, when conducting airways are forming through a process of branching morphogenesis. Expression of factors that inhibi t cellular adhesion might also modulate branching morphogenesis. SPARC is a secreted glycoprotein that exhibits antiadhesive effects on cult ured cells and is widely expressed in embryonic tissues. In this repor t, we examine the distribution of SPARC in fetal rat lung during devel opment and its effect on the process of branching morphogenesis. Immun ohistochemistry and in situ hybridization studies revealed that SPARC was present in the airway epithelial cells during the pseudoglandular stage of lung development, and in blood vessels and smooth muscle cell s associated with airways during the canalicular and saccular stages o f development. We used an in vitro model of rat lung branching morphog enesis to examine airway branching in the presence of: a) a neutralizi ng anti-SPARC antibody; or b) a synthetic peptide from a region of SPA RC that, like the native protein, perturbs cell adhesion and diminishe s the synthesis of fibronectin and thrombospondin 1. Lungs cultured in the presence of either reagent exhibited diminished branching and an abnormal morphology that was characterized in part by dilated airways. These findings implicate SPARC in the development of the airways.