机构：[1]Department of Pulmonary and Critical Care Medicine, China‑Japan Friendship School of Clinical Medicine, Peking University, Beijing 100029[2]Department of Medical Research, Beijing Chao‑Yang Hospital, Beijing 100020[3]Department of Surgical Intensive Care Unit, Beijing An‑Zhen Hospital, Capital Medical University, Beijing 100029[4]Department of Genetics and Cellular Biology, College of Life Sciences, Nankai University, Tianjin 300071[5]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China‑Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Peking University Health Science Center, Beijing 100029, P.R. China
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by progressive lung scarring and excessive extracellular matrix depositon. When stimulated, alveolar epithelial cells (AECs) are aberrantly activated, the expression of profibrotic molecules is enhanced, and lung fibrosis is promoted, but the mechanism for this is unclear. It has been reported that a downregulation of the Na,K-ATPase 1 subunit in renal epithelial cells is involved in renal fibrosis development, but the role of this protein in lung fibrosis remains unknown. In the present study, the expression of the Na,K-ATPase 1 subunit was revealed to be markedly decreased in AECs of patients with IPF and a bleomycin-induced pulmonary fibrosis mouse model. Treatment with transforming growth factor -1 led to significantly downregulation of the Na,K-ATPase 1 subunit in lung adenocarcioma A549 cells. Furthermore, the knockdown of the Na,K-ATPase 1 subunit in A549 cells resulted in the upregulation of profibrotic molecules, activation of the neurogenic locus notch homolog protein 1 and extracellular signal-regulated kinase 1/2 signaling pathways and induction of endoplasmic reticulum stress. These findings reveal that the downregulation of the Na,K-ATPase 1 subunit enhances the expression of profibrotic molecules in AECs and may contribute to IPF pathogenesis.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81430001, 81470258]
第一作者机构：[1]Department of Pulmonary and Critical Care Medicine, China‑Japan Friendship School of Clinical Medicine, Peking University, Beijing 100029
通讯作者：
通讯机构：[1]Department of Pulmonary and Critical Care Medicine, China‑Japan Friendship School of Clinical Medicine, Peking University, Beijing 100029[5]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China‑Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Peking University Health Science Center, Beijing 100029, P.R. China[*1]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China‑Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Peking University Health Science Center, 2 Yinghuayuan Dongjie, Beijing 100029, P.R. China
推荐引用方式(GB/T 7714)：
Li Biyun,Huang Xiaoxi,Xu Xuefeng,et al.The profibrotic effect of downregulated Na,K-ATPase 1 subunit in alveolar epithelial cells during lung fibrosis[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2019,44(1):273-280.doi:10.3892/ijmm.2019.4201.
APA：
Li, Biyun,Huang, Xiaoxi,Xu, Xuefeng,Ning, Wen,Dai, Huaping&Wang, Chen.(2019).The profibrotic effect of downregulated Na,K-ATPase 1 subunit in alveolar epithelial cells during lung fibrosis.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,44,(1)
MLA：
Li, Biyun,et al."The profibrotic effect of downregulated Na,K-ATPase 1 subunit in alveolar epithelial cells during lung fibrosis".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 44..1(2019):273-280
