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10.1172/jci.insight.202475
1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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Shigemura, M.
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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Cummins, E.
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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Seeger, W.
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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Welch, L.
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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1Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
2The Cardio-Pulmonary Institute Justus Liebig University Giessen German Cent, Universities of Giessen & Marburg Lung Center, Giessen, Germany
3Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
4Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
5Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
6Department of Human Genetics, University of Chicago, Chicago, United States of America
7Department of Biochemistry and Molecular Biology, Universidad de Extremadura, Badajoz, Spain
8School of Medicine, University College Dublin, Dublin, Ireland
9Department of Internal Medicine II, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany
10Institute of Pathology, Justus Liebig University, Giessen, Germany
11Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America
12Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, chicago, United States of America
13Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Justus Liebig University, Giessen, Germany
14Department of Pharmacology, Feinberg School of Medicine, Northwestern University, chicago, United States of America
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Published July 16, 2026 - More info
Hypercapnia, elevated carbon dioxide (CO2), is common in advanced chronic obstructive pulmonary disease (COPD) and predicts poor clinical outcomes. Traditionally considered a consequence of disease severity, hypercapnia may drive disease progression by promoting airway dysfunction. Here, we show that hypercapnia acts as an active stressor, driving airway smooth muscle (ASM) constriction through a stromal interaction molecule 1 (STIM1)-dependent pathway. Hypercapnia rapidly activates ERK, triggering sarcoplasmic reticulum calcium (Ca2+) release via phosphorylation of the inositol 1,4,5-trisphosphate receptor. ERK also induces nuclear translocation of the transcription factor c-Fos, enhancing STIM1 transcription. These responses were observed under both supraphysiological (~120 mmHg) and clinically relevant (50-60 mmHg) hypercapnia. Increased STIM1 abundance sustains store-operated Ca2+ entry (SOCE), amplifying ASM signaling. In mice, hypercapnia increased ASM and airway contractility in a STIM1-dependent manner. Human genetic analyses revealed noncoding STIM1 variants associated with reduced lung expression that were enriched in COPD patients. These variants correlated with lower airway resistance under normocapnia; however, this benefit was lost during hypercapnia, indicating a potential gene–environment interaction. Together, our findings position STIM1 as a key mechanistic node linking hypercapnia to Ca2+ dysregulation and airway obstruction, defining a CO2–ERK–STIM1–SOCE axis with translational relevance to chronic lung disease.