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miR449 protects airway regeneration by controlling AURKA/HDAC6-mediated ciliary disassembly

Merit Wildung, Christian Herr, Dietmar Riedel, Cornelia Wiedwald, Alena Moiseenko, Fidel Ramirez, Hataitip Tasena, Maren Heimerl, Mihai Alevra, Naira Movsisyan, et al.
(2022) INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 23(14).
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Abstract
Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449(-/-) mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449(-/-) mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449(-/-) mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449(-/-) cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis.
Keywords
miR449a, microRNA, CDC20B, lung, airway, ciliogenesis, miR449, COPD

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MLA
Wildung, Merit, et al. “MiR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 23, no. 14, 2022, doi:10.3390/ijms23147749.
APA
Wildung, M., Herr, C., Riedel, D., Wiedwald, C., Moiseenko, A., Ramirez, F., … Lize, M. (2022). miR449 protects airway regeneration by controlling AURKA/HDAC6-mediated ciliary disassembly. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(14). https://doi.org/10.3390/ijms23147749
Chicago author-date
Wildung, Merit, Christian Herr, Dietmar Riedel, Cornelia Wiedwald, Alena Moiseenko, Fidel Ramirez, Hataitip Tasena, et al. 2022. “MiR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 (14). https://doi.org/10.3390/ijms23147749.
Chicago author-date (all authors)
Wildung, Merit, Christian Herr, Dietmar Riedel, Cornelia Wiedwald, Alena Moiseenko, Fidel Ramirez, Hataitip Tasena, Maren Heimerl, Mihai Alevra, Naira Movsisyan, Maike Schuldt, Larisa Volceanov-Hahn, Sharen Provoost, Tabea Noethe-Menchen, Diana Urrego, Bernard Freytag, Julia Wallmeier, Christoph Beisswenger, Robert Bals, Maarten van den Berge, Wim Timens, Pieter S. Hiemstra, Corry-Anke Brandsma, Tania Maes, Stefan Andreas, Irene H. Heijink, Luis A. Pardo, and Muriel Lize. 2022. “MiR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 (14). doi:10.3390/ijms23147749.
Vancouver
1.
Wildung M, Herr C, Riedel D, Wiedwald C, Moiseenko A, Ramirez F, et al. miR449 protects airway regeneration by controlling AURKA/HDAC6-mediated ciliary disassembly. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2022;23(14).
IEEE
[1]
M. Wildung et al., “miR449 protects airway regeneration by controlling AURKA/HDAC6-mediated ciliary disassembly,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 23, no. 14, 2022.
@article{01GJ09EMHE31A7Z0RMY7TK6BKF,
  abstract     = {{Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449(-/-) mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449(-/-) mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449(-/-) mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449(-/-) cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis.}},
  articleno    = {{7749}},
  author       = {{Wildung, Merit and  Herr, Christian and  Riedel, Dietmar and  Wiedwald, Cornelia and  Moiseenko, Alena and  Ramirez, Fidel and  Tasena, Hataitip and  Heimerl, Maren and  Alevra, Mihai and  Movsisyan, Naira and  Schuldt, Maike and  Volceanov-Hahn, Larisa and Provoost, Sharen and  Noethe-Menchen, Tabea and  Urrego, Diana and  Freytag, Bernard and  Wallmeier, Julia and  Beisswenger, Christoph and  Bals, Robert and  van den Berge, Maarten and  Timens, Wim and  Hiemstra, Pieter S. and  Brandsma, Corry-Anke and Maes, Tania and  Andreas, Stefan and  Heijink, Irene H. and  Pardo, Luis A. and  Lize, Muriel}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{miR449a,microRNA,CDC20B,lung,airway,ciliogenesis,miR449,COPD}},
  language     = {{eng}},
  number       = {{14}},
  pages        = {{28}},
  title        = {{miR449 protects airway regeneration by controlling AURKA/HDAC6-mediated ciliary disassembly}},
  url          = {{http://doi.org/10.3390/ijms23147749}},
  volume       = {{23}},
  year         = {{2022}},
}
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