KLF2 and caveolin-1 as early indicators of acute lung injury induced by paraquat

Eur Rev Med Pharmacol Sci. 2016;20(1):138-45.

Abstract

Objective: The roles of Krüppel-like factors KLF2 and KLF4, and caveolin-1 (Cav-1) in acute lung injury (ALI) induced by paraquat (PQ) are insufficiently defined. Here we tested their expression in a rat model of ALI.

Materials and methods: 80 Wistar rats were divided into control group and groups exposed to PQ for 6, 12, and 24 hours (20 animals/group). ALI was assessed by behavioural and pathological scores. In addition, we quantified the concentration of KLF2, KLF4, and Cav-1 in serum by ELISA, and expression of these proteins at the mRNA and protein level in lung tissue (respectively, qPCR and Western blot).

Results: Pathological scores were the highest at 12 hours after exposure to PQ. These changes correlated well with the kinetics of serum levels of KLF2, KLF4 and Cav-1. Thus, the lowest levels of the two former proteins were observed at 12 hours post-exposure, whereas Cav-1 levels peaked at this time point. In lung tissue, the kinetics of mRNA and protein expression of these proteins was different from the changes in the serum. Specifically, both KLF and Cav-1 mRNA expression changed significantly at 6 hours post-exposure to PQ, whereas KLF4 mRNA expression did not change significantly at any of the studied time points. Studies of at the protein level corroborated the observations of mRNA kinetics.

Conclusions: We demonstrate here that lung tissue expression of KLF2 and Cav-1 is modulated early in the pathogenesis of ALI. These proteins could, therefore, serve as molecular markers for early diagnosis of this clinical condition.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism*
  • Animals
  • Caveolin 1 / biosynthesis*
  • Disease Models, Animal
  • Herbicides / adverse effects*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Paraquat / adverse effects*
  • Rats
  • Rats, Wistar

Substances

  • Caveolin 1
  • Herbicides
  • Klf2 protein, rat
  • Klf4 protein, rat
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Paraquat