The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury

Respir Res. 2016 Dec 7;17(1):164. doi: 10.1186/s12931-016-0480-y.

Abstract

Background: Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown.

Methods: Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells.

Results: The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation.

Conclusions: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.

Keywords: Acute lung injury; Cellular kinetics; Regeneration; Type 1 alveolar epithelial cells; Type 2 alveolar epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology*
  • Acute Lung Injury / physiopathology
  • Animals
  • Cell Proliferation* / drug effects
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Hepatocyte Growth Factor / metabolism
  • Indoles / pharmacology
  • Kinetics
  • Lipopolysaccharides
  • Male
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / metabolism
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology*
  • Pulmonary Alveoli / physiopathology
  • Rats, Sprague-Dawley
  • Regeneration* / drug effects
  • Signal Transduction
  • Sulfonamides / pharmacology

Substances

  • ((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)
  • Indoles
  • Lipopolysaccharides
  • Piperazines
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met