RT Journal Article SR Electronic T1 Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis JF ERJ Open Research JO erjor FD European Respiratory Society SP 00191-2022 DO 10.1183/23120541.00191-2022 VO 8 IS 4 A1 Jade Jaffar A1 Mae Wong A1 Gregory A. Fishbein A1 Monther Alhamdoosh A1 Laura McMillan A1 Cristina Gamell-Fulla A1 Milica Ng A1 Nick Wilson A1 Karen Symons A1 Ian Glaspole A1 Glen Westall YR 2022 UL http://openres.ersjournals.com/content/8/4/00191-2022.abstract AB Introduction 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.Methods 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+ cells were quantified using multiplex immunohistochemistry. Protein expression of MMP7 in whole lung lysates was quantified by Western blotting. Bulk tissue transcriptomic profiles of 101 samples were analysed using RNA sequencing technologies.Results 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.Conclusions 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.This study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially nonepithelial or immune-cell source https://bit.ly/3QsXYFP