Regenerative therapy based on miRNA-302 mimics for enhancing host recovery from pneumonia caused by Streptococcus pneumoniae

Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8493-8498. doi: 10.1073/pnas.1818522116. Epub 2019 Apr 10.


Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide. A defining feature of pneumonia is lung injury, leading to protracted suffering and vulnerability long after bacterial clearance. Little is known about which cells are damaged during bacterial pneumonia and if the regenerative process can be harnessed to promote tissue repair and host recovery. Here, we show that infection of mice with Streptococcus pneumoniae (Sp) caused substantial damage to alveolar epithelial cells (AEC), followed by a slow process of regeneration. Concurrent with AEC regeneration, the expression of miRNA-302 is elevated in AEC. Treatment of Sp-infected mice with miRNA-302 mimics improved lung functions, host recovery, and survival. miRNA-302 mediated its therapeutic effects, not by inhibiting apoptosis and preventing damage, but by promoting proliferation of local epithelial progenitor cells to regenerate AEC. These results demonstrate the ability of microRNA-based therapy to promote AEC regeneration and enhance host recovery from bacterial pneumonia.

Keywords: alveolus; bacteria; miRNA; pneumonia; regeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology
  • Animals
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Lung / drug effects
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology*
  • Pneumonia, Pneumococcal / metabolism
  • Pneumonia, Pneumococcal / physiopathology*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Double-Stranded / pharmacology
  • Regeneration / drug effects*
  • Streptococcus pneumoniae


  • MicroRNAs
  • RNA, Double-Stranded