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A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis

Richard Y. Kim, Krishna P. Sunkara, Ken R. Bracke, Andrew G. Jarnicki, Chantal Donovan, Alan C. Hsu, Antonio Ieni, Emma L. Beckett, Izabela Galvão, Sara Wijnant, et al.
(2021) SCIENCE TRANSLATIONAL MEDICINE. 13(621).
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Abstract
Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease.
Keywords
General Medicine, Microbiology, Food Science, FACTOR-KAPPA-B, RESPIRATORY-INFECTION, ANIMAL-MODELS, KEY FEATURES, INFLAMMATION, PROTEIN, MIR-21, S100A9, EXPRESSION, BINDING

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MLA
Kim, Richard Y., et al. “A MicroRNA-21–Mediated SATB1/S100A9/NF-ΚB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis.” SCIENCE TRANSLATIONAL MEDICINE, vol. 13, no. 621, 2021, doi:10.1126/scitranslmed.aav7223.
APA
Kim, R. Y., Sunkara, K. P., Bracke, K. R., Jarnicki, A. G., Donovan, C., Hsu, A. C., … Hansbro, P. M. (2021). A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis. SCIENCE TRANSLATIONAL MEDICINE, 13(621). https://doi.org/10.1126/scitranslmed.aav7223
Chicago author-date
Kim, Richard Y., Krishna P. Sunkara, Ken R. Bracke, Andrew G. Jarnicki, Chantal Donovan, Alan C. Hsu, Antonio Ieni, et al. 2021. “A MicroRNA-21–Mediated SATB1/S100A9/NF-ΚB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis.” SCIENCE TRANSLATIONAL MEDICINE 13 (621). https://doi.org/10.1126/scitranslmed.aav7223.
Chicago author-date (all authors)
Kim, Richard Y., Krishna P. Sunkara, Ken R. Bracke, Andrew G. Jarnicki, Chantal Donovan, Alan C. Hsu, Antonio Ieni, Emma L. Beckett, Izabela Galvão, Sara Wijnant, Fabio LM. Ricciardolo, Antonino Di Stefano, Tatt Jhong Haw, Gang Liu, Angela L. Ferguson, Umamainthan Palendira, Peter A. Wark, Griet Conickx, Pieter Mestdagh, Guy Brusselle, Gaetano Caramori, Paul S. Foster, Jay C. Horvat, and Philip M. Hansbro. 2021. “A MicroRNA-21–Mediated SATB1/S100A9/NF-ΚB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis.” SCIENCE TRANSLATIONAL MEDICINE 13 (621). doi:10.1126/scitranslmed.aav7223.
Vancouver
1.
Kim RY, Sunkara KP, Bracke KR, Jarnicki AG, Donovan C, Hsu AC, et al. A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis. SCIENCE TRANSLATIONAL MEDICINE. 2021;13(621).
IEEE
[1]
R. Y. Kim et al., “A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis,” SCIENCE TRANSLATIONAL MEDICINE, vol. 13, no. 621, 2021.
@article{8743628,
  abstract     = {{Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease.}},
  articleno    = {{eaav7223}},
  author       = {{Kim, Richard Y. and Sunkara, Krishna P. and Bracke, Ken R. and Jarnicki, Andrew G. and Donovan, Chantal and Hsu, Alan C. and Ieni, Antonio and Beckett, Emma L. and Galvão, Izabela and Wijnant, Sara and Ricciardolo, Fabio LM. and Di Stefano, Antonino and Haw, Tatt Jhong and Liu, Gang and Ferguson, Angela L. and Palendira, Umamainthan and Wark, Peter A. and Conickx, Griet and Mestdagh, Pieter and Brusselle, Guy and Caramori, Gaetano and Foster, Paul S. and Horvat, Jay C. and Hansbro, Philip M.}},
  issn         = {{1946-6234}},
  journal      = {{SCIENCE TRANSLATIONAL MEDICINE}},
  keywords     = {{General Medicine,Microbiology,Food Science,FACTOR-KAPPA-B,RESPIRATORY-INFECTION,ANIMAL-MODELS,KEY FEATURES,INFLAMMATION,PROTEIN,MIR-21,S100A9,EXPRESSION,BINDING}},
  language     = {{eng}},
  number       = {{621}},
  pages        = {{16}},
  title        = {{A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis}},
  url          = {{http://doi.org/10.1126/scitranslmed.aav7223}},
  volume       = {{13}},
  year         = {{2021}},
}
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