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

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.