Contribution of meprin β in lung fibrosis

Introduction: Lung fibrosis is a severe disease which is characterized by collagen deposition and stiffening of the lung. Over-expression of the transcription factor fra-2 in mice (fra-2 tg) leads to an increase of the inflammatory infiltrate, pro-fibrogenic factors and to development of lung fibrosis, which resembled the human idiopathic pulmonary fibrosis (IPF). The protease meprin β is the most upregulated gene in the lung of fra-2 tg mice. In addition, meprin β has been previously shown to enhance maturation of collagen. Therefore, we speculate that meprin β is an important player in lung fibrosis.

Methods and Results: In this study we observed that meprin β was elevated in lung of mice exposed to the fibrotic drug, bleomycin. The increased expression was most prominent after 10 – 14 days administration and reduced gradually in the later time point. The mRNA and protein levels of meprin β were elevated in mouse epithelial cells isolated after 14 days bleomycin administration. Accordingly, the protein level of meprin β was increased in human lung fibrosis in comparison to donor samples. The expression of meprin β was mostly confined to epithelial cells, suggesting that these cells might be the source of meprin β in lung fibrosis. In vitro experiments revealed that human epithelial A549 cells stimulated with TGF-β released meprin β in the cell supernatant, suggesting an induction of a shedding process. Shedding of meprin β can affect surrounding cells in a paracrine manner.

Conclusion: In conclusion, these data showed a possible role of meprin β in mediating the fibrotic process on epithelial cells and fibroblasts. However, further studies are needed to better elucidate the role of meprin β in the lung fibrosis.