Increase of bone morphogenetic protein-7 expressing pulmonary resident cells in pneumonectomized rats

Compensatory lung growth (CLG) is recognized in rodents subjected to major pulmonary resection; however, the source of cells constituting regenerated tissues during the CLG is still unknown. We investigated the differentiation of lung resident cells and the participation of bone marrow (BM)-derived cells in the remnant lung of pneumonectomized rats.

After left pneumonectomy, the right remnant lung of Wistar rats was subjected to morphologic and molecular experiments at several time points. We studied the expression of bone morphogenic protein 7 (BMP-7), an accelerator of epithelial differentiation, based on the gene expression profile data of the remnant lung. Next, we evaluated the presence of GFP-positive cells in the remnant lung of Wistar rats that had received BM transplantation from green fluorescent protein (GFP) gene-transgenic Wistar rats prior to left pneumonectomy.

We observed progression of emphysematous change, modulation of gene expression profile, and proliferating cellular nuclear antigen-positive cells in the alveoli of the remnant lungs. BMP-7 protein positive cells were detected in the alveolar septa, which increased significantly over time with the progression of emphysematous change. No bone marrow-derived cells were detected in the right remnant lung of the GFP-BM transferred rats by fluorescence microscopy, immunohistochemistry, or polymerase chain reaction at any time.

Lung resident cells appear to contribute to CLG, possibly via a trans-differentiation pathway.