Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) is a protein secreted by epithelial cells in IPF lungs. It is not known if MMP7 expression correlates with fibrotic changes in lung tissue. Tissue samples from lung apices and bases were obtained from 20 IPF patients and 14 non-diseased control (NDC) donors. In formalin-fixed paraffin-embedded sections, histological assessment of fibrosis was performed; overall MMP7 positivity was assessed by immunohistochemistry and MMP7 Lung tissue from IPF bases was more fibrotic than in apices. MMP7 protein is elevated in IPF lung base tissue. In IPF whole lung lysates, MMP7 protein levels are increased compared to NDC donors and was increased in IPF lung bases compared to apices. MMP7 protein levels correlated with MMP7 gene expression levels in lung tissue. MMP7 transcript levels were increased in IPF base compared to NDC base lung tissue and increased in IPF base tissue compared to IPF apex tissue. Our cross-sectional study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially nonepithelial or immune-cell source. Mechanisms of disease progression in IPF are still unclear, and our study suggests aberrant MMP7 production may be a histological starting point of lung tissue fibrosis.

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Conflict of interest: M. Wong has received support for the present manuscript from CSL; the following disclosures have been made outside the submitted work: employee of CSL Innovations Pty Ltd, who provided support for attending meetings/travel; shareholder of CSL stocks. M. Alhamdoosh has received support for the present manuscript from CSL; the following disclosures have been made outside the submitted work: employee of CSL Limited and shareholder of CSL Limited. L. McMillan has received support for the present manuscript from CSL; the following relationships have been disclosed outside the submitted work: employee of CSL Innovations. C. Gamell-Fulla has received support for the present manuscript from CSL. M. Ng reports the following relationships have been disclosed outside the submitted work: employment contract with CSL and stocks owned in CSL. G. Westall has received support for the present manuscript from CSL; the following relationships have been disclosed outside the submitted work: participation in an Advisory Board Meeting for CSL. The remaining authors have nothing to disclose.