Regulation of human lung alveolar multipotent cells by a novel p38α MAPK/miR-17-92 axis

EMBO J. 2012 Aug 15;31(16):3431-41. doi: 10.1038/emboj.2012.192. Epub 2012 Jul 24.


The cellular and molecular mechanisms that control lung homeostasis and regeneration are still poorly understood. It has been proposed that a population of cells exists in the mouse lung with the potential to differentiate into all major lung bronchioalveolar epithelium cell types in homeostasis or in response to virus infection. A new population of E-Cad/Lgr6(+) putative stem cells has been isolated, and indefinitely expanded from human lungs, harbouring both, self-renewal capacity and the potency to differentiate in vitro and in vivo. Recently, a putative population of human lung stem cells has been proposed as being c-Kit(+). Unlike Integrin-α6(+) or c-Kit(+) cells, E-Cad/Lgr6(+) single-cell injections in the kidney capsule produce differentiated bronchioalveolar tissue, while retaining self-renewal, as they can undergo serial transplantations under the kidney capsule or in the lung. In addition, a signalling network involving the p38α pathway, the activation of p53 and the regulation of the miR-17-92 cluster has been identified. Disruption of the proper cross-regulation of this signalling axis might be involved in the promotion of human lung diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Lung / cytology*
  • MicroRNAs / metabolism*
  • Microscopy, Fluorescence
  • Signal Transduction
  • Stem Cells / physiology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • MIRN17 microRNA, human
  • MIRN19 microRNA, human
  • MicroRNAs
  • p38 Mitogen-Activated Protein Kinases