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Published on: January 6, 2015
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Deficiency in DDR1 Induces Pulmonary Hypertension and Impaired Alveolar Development
Quinn A Bonafiglia1,2, Yu-Qing Zhou2, Guangpei Hou1,2
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
American Journal of Respiratory Cell and Molecular Biology
|August 4, 2022
Summary
Discoidin domain receptor 1 (DDR1) is crucial for lung development and alveolarization. DDR1 deficiency in mice leads to pulmonary hypertension and bronchopulmonary dysplasia, highlighting its role in preventing these conditions.
Area of Science:
- Cell biology
- Developmental biology
- Pulmonary medicine
Background:
- Pulmonary hypertension (PH) is a severe condition often linked to right ventricular failure.
- Bronchopulmonary dysplasia (BPD) in infants can cause secondary PH and high mortality.
- The role of discoidin domain receptor 1 (DDR1) in lung development and PH is not understood.
Purpose of the Study:
- To investigate the function of DDR1 in lung development.
- To determine if DDR1 deficiency contributes to pulmonary hypertension and BPD pathogenesis.
- To explore the mechanisms by which DDR1 influences alveolar epithelial cells.
Main Methods:
- Utilized a mouse model with DDR1 deletion (Ddr1 mice).
- Conducted pathological analysis of lung tissue for alveolar development and vascular changes.
- Performed gene expression analysis to assess alveologenesis and epithelial-to-mesenchymal transition (EMT) markers.
- Conducted in vitro mechanistic studies on alveolar epithelial cells.
Main Results:
- DDR1-deficient mice exhibited increased mortality (35%) between 1-4 months of age.
- DDR1 deficiency led to reduced right ventricular contractility and distal pulmonary artery muscularization, indicative of PH.
- Impaired alveolar development, characterized by enlarged alveolar spaces, was observed in Ddr1 mice.
- Reduced expression of alveologenesis factors and EMT markers was found in Ddr1 mice.
- In vitro studies confirmed DDR1's role in mediating EMT, migration, and growth of alveolar epithelial cells.
Conclusions:
- DDR1 plays a critical role in mediating alveolarization during lung development.
- DDR1 deficiency results in a novel mouse model of spontaneous PH and BPD.
- Targeting DDR1 may offer therapeutic potential for lung development disorders and PH.
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