Derepression of matrix metalloproteinase gene transcription and an emphysema-like phenotype in transcription factor Zbtb7c knockout mouse lungs

FEBS Lett. 2019 Sep;593(18):2665-2674. doi: 10.1002/1873-3468.13501. Epub 2019 Jun 30.

Abstract

Dysregulated matrix metalloproteinase (MMP) gene expression is a major cause of the degradation of lung tissue that is integral to emphysema pathogenesis. Cigarette smoking (CS) increases MMP gene expression, a major contributor to emphysema development. We previously reported that Zbtb7c is a transcriptional repressor of several Mmp genes (Mmps-8, -10, -13, and -16). Here, we show that Zbtb7c knockout mice have mild emphysema-like phenotypes, including alveolar wall destruction, enlarged alveoli, and upregulated Mmp genes. Alveolar size and Mmp gene expression in Zbtb7c-/- mouse lungs are increased more severely upon exposure to CS, compared to those of Zbtb7c+/+ mouse lungs. These observations suggest that Zbtb7c degradation or absence may contribute to the pathogenesis of emphysema.

Keywords: Zbtb7c (Kr-pok); cigarette smoking; emphysema; matrix metalloproteinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cigarette Smoking / adverse effects
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics*
  • Emphysema / genetics*
  • Gene Knockout Techniques
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology*
  • Matrix Metalloproteinases / genetics*
  • Mice
  • Phenotype*
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics*
  • Transcription, Genetic / genetics*

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • Zbtb7a protein, mouse
  • Matrix Metalloproteinases