Research Papers: Pathology:

Tsp1 promotes alveolar stem cell proliferation and its down-regulation relates to lung inflammation in intralobar pulmonary sequestration

Kuan Li, Qi Wu, Xin Sun, Yan Geng, Dong Leng, Hongwei Li, Subei Zhang, Qiaoxing Wang, Junping Wu, Long Xu, Xue Li, Yu Li, Qiuyang Zhang, Adrianne Kurkciyan, Jiurong Liang, Dianhua Jiang and Huaiyong Chen _

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Oncotarget. 2017; 8:64867-64877. https://doi.org/10.18632/oncotarget.19952

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Kuan Li1,*, Qi Wu2,*, Xin Sun2,*, Yan Geng3, Dong Leng4, Hongwei Li5, Subei Zhang2, Qiaoxing Wang2, Junping Wu5, Long Xu5, Xue Li1, Yu Li1, Qiuyang Zhang1, Adrianne Kurkciyan3, Jiurong Liang3, Dianhua Jiang3 and Huaiyong Chen1,2

1 Department of Basic Medicine, Haihe Clinic College of Tianjin Medical University, Tianjin, China

2 Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin, China

3 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States

4 Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

5 Department of Respiratory Medicine, Tianjin Haihe Hospital, Tianjin, China

* These authors have contributed equally to this work

Correspondence to:

Huaiyong Chen, email:

Dianhua Jiang, email:

Keywords: AT2 cells, intralobar pulmonary sequestration, endothelial, Tsp1, CD36, Pathology Section

Received: February 15, 2017 Accepted: July 20, 2017 Published: August 04, 2017


An aberrant systemic artery supply results in recurrent infections in the abnormal lung lobe of intralobar pulmonary sequestration (ILS). The mechanisms underlying such persistent inflammation are unknown. Here, we hypothesize that alteration of an endothelial cell niche for alveolar epithelial cells results in the impaired proliferation potential of alveolar progenitor cells, leading to the defective defense mechanism in intralobar pulmonary sequestration. Paraffin sections of lung tissues from patients with intralobar pulmonary sequestration or from healthy controls were collected for analysis of alveolar epithelial alterations in intralobar pulmonary sequestration by quantitative RT-PCR or immunofluorescent staining. Differential transcripts were identified between human pulmonary artery endothelial cells and human aortic endothelial cells by microarray. Validation of microarray data by quantitative PCR analysis indicated that thrombospondin-1 expression level is low in near-lesion part but high in lesion part of ILS lobe as compared to healthy controls. In vitro 3-D matrigel culture was adopted to evaluate the regulation of alveolar progenitor cells by thrombospondin-1 and CD36. We found that the proliferative potential of alveolar type 2 stem/progenitor cells was impaired in intralobar pulmonary sequestration. Mechanistically, we discovered that endothelial thrombospondin-1 promotes alveolar type 2 cell proliferation through the interaction with CD36. These data demonstrate that alveolar stem cells are impaired in the abnormal lobe from patients with intralobar pulmonary sequestration and imply that restoring epithelial integrity can be beneficial for the future treatments of recurrent infections in lung pathologies.

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