Am. J. Respir. Cell Mol. Biol., Vol 13, No. 3, 09 1995, 279-287.
SPARC participates in the branching morphogenesis of developing fetal rat lung
TP Strandjord, EH Sage and JG Clark
Department of Pediatrics, University of Washington, Seattle 98195-6320, USA.
Adhesion of cells to components of the extracellular matrix has been shown
to be critical in normal lung development, particularly during the
pseudoglandular stage, when conducting airways are forming through a
process of branching morphogenesis. Expression of factors that inhibit
cellular adhesion might also modulate branching morphogenesis. SPARC is a
secreted glycoprotein that exhibits antiadhesive effects on cultured cells
and is widely expressed in embryonic tissues. In this report, we examine
the distribution of SPARC in fetal rat lung during development and its
effect on the process of branching morphogenesis. Immunohistochemistry 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 cells associated with airways during the
canalicular and saccular stages of development. We used an in vitro model
of rat lung branching morphogenesis to examine airway branching in the
presence of: a) a neutralizing anti-SPARC antibody; or b) a synthetic
peptide from a region of SPARC that, like the native protein, perturbs cell
adhesion and diminishes 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.
