Keratinocyte growth factor-2 is protective in lipopolysaccharide-induced acute lung injury in rats

Respir Physiol Neurobiol. 2014 Sep 15:201:7-14. doi: 10.1016/j.resp.2014.06.011. Epub 2014 Jun 26.

Abstract

Keratinocyte growth factor-2 (KGF-2) plays a key role in lung development, but its role in acute lung injury has not been well characterized. Lipopolysaccharide instillation caused acute lung injury, which significantly elevated lung wet-to-dry weight ratio, protein and neutrophils in bronchoalveolar lavage fluid (BALF), inhibited surfactant protein A and C expression in lung tissue, and increased pathological injury. Pretreatment with KGF-2 improved the above lung injury parameters, partially restored surfactant protein A and C expression, and KGF-2 given 2-3 days before LPS challenge showed maximum lung injury improvement. Pretreatment with KGF-2 also markedly reduced the levels of TNF-α, MIP-2, IL-1β and IL-6 in BALF and the levels of IL-1β and IL-6 in lung tissue. Histological analysis showed there was increased proliferation of alveolar type II epithelial cells in lung parenchyma, which reached maximal 2 days after KGF-2 instillation. Intratracheal administration of KGF-2 attenuates lung injury induced by LPS, suggesting KGF-2 may be potent in the intervention of acute lung injury.

Keywords: Acute lung injury; Epithelial cells; Keratinocyte growth factor-2; Lipopolysaccharide; Pulmonary surfactant proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fibroblast Growth Factor 10 / therapeutic use*
  • Ki-67 Antigen / metabolism
  • Lipopolysaccharides / toxicity*
  • Lung / drug effects
  • Lung / pathology
  • Lung / ultrastructure
  • Male
  • Neutrophils / pathology
  • Peptides / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Cytokines
  • Fibroblast Growth Factor 10
  • Ki-67 Antigen
  • Lipopolysaccharides
  • Peptides
  • RNA, Messenger
  • Sftpc protein, rat