ORIGINAL ARTICLE Increase of bone morphogenetic protein-7 expressing pulmonary resident cells in pneumonectomized rats Taro Ohba • Hironobu Wada • Ichiro Yoshino • Shigetoshi Yoshida • Tetsuzo Tagawa • Fumihiro Shoji • Koji Yamazaki • Yoshihiko Maehara Received: 25 August 2012 / Accepted: 9 December 2012 Ó Springer Japan 2013 Abstract Purpose Compensatory lung growth (CLG) is recognized in rodents subjected to major pulmonary resection; how- ever, 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 Wi- star rats prior to left pneumonectomy. Results We observed progression of emphysematous change, modulation of gene expression profile, and pro- liferating 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 emphyse- matous change. No bone marrow-derived cells were detected in the right remnant lung of the GFP-BM trans- ferred rats by fluorescence microscopy, immunohisto- chemistry, or polymerase chain reaction at any time. Conclusion Lung resident cells appear to contribute to CLG, possibly via a trans-differentiation pathway. Keywords Lung Á Bone morphogenic protein-7 (BMP-7) Á Compensatory lung growth Abbreviations BMT Bone marrow transplantation WB Western blotting IHC Immunohistochemistry MET Mesenchymal-epithelial transition EMT Epithelial-mesenchymal transition Introduction The remnant lung of rodents subjected to major pulmonary resection undergoes compensatory growth, which restores the weight, volume, DNA, and protein of the residual organs [1–3]. Mechanical stretching caused by the differ- ence between the residual lung volume and pleural capacity could be a trigger of the compensatory lung growth (CLG) [1, 3]; however, the subsequent dynamic process of molecular events remains to be clarified. The remnant lung exhibits enlarged air space per single alveoli, resembling chronic pulmonary emphysema, so the alveolar tissue is not fully compensated. A better understanding of the mecha- nism of CLG may contribute to the development of regenerative medicine for pulmonary dysfunction after surgery, as well as for chronic pulmonary diseases. T. Ohba and H. Wada contributed equally to this study, and both are credited as the first authors. T. Ohba (&) Á T. Tagawa Á F. Shoji Á K. Yamazaki Á Y. Maehara Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan e-mail: taro.oba@gmail.com H. Wada Á I. Yoshino Á S. Yoshida Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 123 Surg Today DOI 10.1007/s00595-013-0604-7