PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Lung resident cells appear to contribute to CLG, possibly via a trans-differentiation pathway.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Lung resident cells appear to contribute to CLG, possibly via a trans-differentiation pathway.
Authors: Elisabeth M Zeisberg; Oleg Tarnavski; Michael Zeisberg; Adam L Dorfman; Julie R McMullen; Erika Gustafsson; Anil Chandraker; Xueli Yuan; William T Pu; Anita B Roberts; Eric G Neilson; Mohamed H Sayegh; Seigo Izumo; Raghu Kalluri Journal: Nat Med Date: 2007-07-29 Impact factor: 53.440