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SPARC participates in the branching morphogenesis of developing fetal rat lung
T P Strandjord1, E H Sage, J G Clark
1Department of Pediatrics, University of Washington, Seattle 98195-6320, USA.
Abstract:
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.
Insights
Secreted protein acidic and rich in cysteine (SPARC) is crucial for normal lung development. Inhibiting SPARC disrupts airway branching morphogenesis, leading to abnormal lung structure.
Area of Science:
- Developmental Biology
- Cell Biology
- Extracellular Matrix Biology
Background:
- Cellular adhesion to the extracellular matrix is vital for lung development, especially during airway branching morphogenesis.
- Secreted protein acidic and rich in cysteine (SPARC), a glycoprotein with anti-adhesive properties, is expressed in embryonic tissues.
Purpose of the Study:
- To investigate the distribution of SPARC in fetal rat lung development.
- To determine the effect of SPARC on airway branching morphogenesis.
Main Methods:
- Immunohistochemistry and in situ hybridization to map SPARC expression.
- In vitro culture of rat lungs with anti-SPARC antibody or SPARC-derived peptide.
Main Results:
- SPARC is expressed in airway epithelial cells during the pseudoglandular stage and in associated vascular and smooth muscle cells later in development.
- Inhibition of SPARC function in vitro led to reduced airway branching and dilated airways.
- SPARC inhibition also affected fibronectin and thrombospondin 1 synthesis.
Conclusions:
- SPARC plays a significant role in regulating airway branching morphogenesis during lung development.
- SPARC's anti-adhesive properties are critical for normal lung structural formation.
- Targeting SPARC may offer insights into developmental lung disorders.