Runt-Related Transcription Factor 1 Regulates LPS-Induced Acute Lung Injury via NF-κB Signaling.
Runt-related transcription factor 1 (RUNX1), a transcription factor expressed in multiple organs, plays important roles in embryonic development and hematopoiesis. Although RUNX1 is highly expressed in pulmonary tissues, its roles in lung function and homeostasis are unknown. We sought to assess the role of RUNX1 in lung development and inflammation after LPS challenge. Expression of RUNX1 was assessed in the developing and postnatal lung. RUNX1 was conditionally deleted in pulmonary epithelial cells. Pulmonary maturation was evaluated in the developing and postnatal lung, and lung inflammation was investigated in adult mice after LPS challenge. Interactions between RUNX1 and inflammatory signaling via NF-κB-IkB kinase β were assessed in vitro. RUNX1 was expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung. The RUNX1 gene was efficiently deleted from respiratory epithelial cells producing Runx1∆/∆mice. Although lung maturation was delayed, Runx1∆/∆mice survived postnatally and subsequent growth and maturation of the lung proceeded normally. Increased respiratory distress, inflammation, and proinflammatory cytokines were observed in the Runx1-deleted mice after pulmonary LPS exposure. RUNX1 deletion was associated with the activation of NF-κB in respiratory epithelial cells. RUNX1 was required for the suppression of NF-κB signaling pathway via inhibition of IkB kinase β in in vitro studies. RUNX1 plays a critical role in the lung inflammation after LPS-induced injury.
1 Department of Respiratory Medicine.|2 Laboratory of Cardiovascular Diseases, Research Center of Regeneration Medicine, and.
Xiaoju
X
Tang
2 Laboratory of Cardiovascular Diseases, Research Center of Regeneration Medicine, and.
Ling
L
Sun
3 Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, China.
Xiaodong
X
Jin
1 Department of Respiratory Medicine.
Yifan
Y
Chen
1 Department of Respiratory Medicine.
Hui
H
Zhu
4 First Affiliated Hospital of Kunming Medical University, Kunming, China.
Yasha
Y
Liang
1 Department of Respiratory Medicine.
Qingbo
Q
Wu
5 Fourth People's Hospital of Sichuan Province, Chengdu, China.
Xing
X
Han
6 Department of Respiratory Medicine, Fourth Military Medical University, Xian, China.
Jianing
J
Liang
2 Laboratory of Cardiovascular Diseases, Research Center of Regeneration Medicine, and.
Xiaojing
X
Liu
1 Department of Respiratory Medicine.
Zongan
Z
Liang
1 Department of Respiratory Medicine.
Gang
G
Wang
1 Department of Respiratory Medicine.
Fengming
F
Luo
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D056809:Alveolar Epithelial Cells / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
D050676:Core Binding Factor Alpha 2 Subunit; D004731:Endotoxins; D016328:NF-kappa B; C493726:Runx1 protein, mouse; C044101:endotoxin, Escherichia coli; D051550:I-kappa B Kinase
AML1/Runt-related transcription factor 1; IkB kinase β; NF-κB; acute lung injury; respiratory epithelium