Alveologenesis is the last step of lung maturation and generates ~95% of the gas- exchange surface area through formation of new septa. Disruption of alveologenesis, such as in bronchopulmonary dysplasia (BPD), leads to simplified alveoli, poor gas exchange and other respiratory deficiencies later in life. Myofibroblasts represents a key cell type in alveologenesis. In conventional two-dimensional analysis, myofibroblasts are depicted as dots at the tip of the finger-like septal crest, and are postulated to drive new septa formation by migrating into the lumen. We have found from three-dimensional analysis, that myofibroblasts are interconnected into rings, and rings are interconnected into nets. We postulate that it is the tensile property of this network of myofibroblasts that drive new septa formation. In mouse models of human lung development and disease, we will use genetic tools to investigate the role of myofibroblasts in normal alveologenesis, in alveolar simplification in BPD, and in regeneration of new septa after premature birth and BPD.
Bronchopulmonary Dysplasia is a prevalent lung disease that affect premature infants, with 12,000 new cases diagnosed in the US each year. The goal of this study is to test the hypothesis that the proper control of the number, organization, as well as tensile property of alveolar myofibroblasts is essential for generating new gas-exchange surface area. Our findings will provide insights for more effective treatment of BPD as well as how to regenerate gas-exchange surfaces in premature lungs.
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