title: MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration.
abstract: The pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX)-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung.
authors: College of Life Sciences, Peking University, Beijing 100871, China; National Institute of Biological Sciences, Beijing 102206, China.
authors: Zhe
authors: Z
authors: Liu
authors: National Institute of Biological Sciences, Beijing 102206, China; College of Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Huijuan
authors: H
authors: Wu
authors: National Institute of Biological Sciences, Beijing 102206, China; College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors: Kewu
authors: K
authors: Jiang
authors: National Institute of Biological Sciences, Beijing 102206, China; College of Life Sciences, Tsinghua University, Beijing 100084, China.
authors: Yanjie
authors: Y
authors: Wang
authors: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China; Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China.
authors: Wenjing
authors: W
authors: Zhang
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Qiqi
authors: Q
authors: Chu
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Juan
authors: J
authors: Li
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Huanwei
authors: H
authors: Huang
authors: National Institute of Biological Sciences, Beijing 102206, China.
authors: Tao
authors: T
authors: Cai
authors: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China; Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 200120, China.
authors: Hongbin
authors: H
authors: Ji
authors: Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering, Tsinghua University, Beijing 100084, China.
authors: Chun
authors: C
authors: Yang
authors: National Institute of Biological Sciences, Beijing 102206, China. Electronic address: tangnan@nibs.ac.cn.
authors: Nan
authors: N
authors: Tang
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics* / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001696:Biomechanical Phenomena; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011013:Pneumonectomy; D061251:Primary Cell Culture; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D011725:Pyridines / Q000494:pharmacology; D012038:Regeneration / Q000235:genetics*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; C581598:Cdc42 protein, mouse; D018797:Cell Cycle Proteins; D007093:Imidazoles; D010750:Phosphoproteins; D011725:Pyridines; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C432165:pyrazolanthrone; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020764:cdc42 GTP-Binding Protein; C093642:SB 203580