Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis
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 Tissu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
European Respiratory Society
2022-10-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/8/4/00191-2022.full |
| _version_ | 1797809412577951744 |
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| author | Jade Jaffar Mae Wong Gregory A. Fishbein Monther Alhamdoosh Laura McMillan Cristina Gamell-Fulla Milica Ng Nick Wilson Karen Symons Ian Glaspole Glen Westall |
| author_facet | Jade Jaffar Mae Wong Gregory A. Fishbein Monther Alhamdoosh Laura McMillan Cristina Gamell-Fulla Milica Ng Nick Wilson Karen Symons Ian Glaspole Glen Westall |
| author_sort | Jade Jaffar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:52:20Z |
| format | Article |
| id | doaj.art-100231e77cc2445ab07eb39a4bc2833d |
| institution | Directory Open Access Journal |
| issn | 2312-0541 |
| language | English |
| last_indexed | 2024-03-13T06:52:20Z |
| publishDate | 2022-10-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj.art-100231e77cc2445ab07eb39a4bc2833d2023-06-07T13:30:36ZengEuropean Respiratory SocietyERJ Open Research2312-05412022-10-018410.1183/23120541.00191-202200191-2022Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosisJade Jaffar0Mae Wong1Gregory A. Fishbein2Monther Alhamdoosh3Laura McMillan4Cristina Gamell-Fulla5Milica Ng6Nick Wilson7Karen Symons8Ian Glaspole9Glen Westall10 Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia CSL Limited, Parkville, VIC, Australia David Geffen School of Medicine at UCLA, Los Angeles, CA, USA CSL Limited, Parkville, VIC, Australia CSL Limited, Parkville, VIC, Australia CSL Limited, Parkville, VIC, Australia CSL Limited, Parkville, VIC, Australia CSL Limited, Parkville, VIC, Australia Department of Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia 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.http://openres.ersjournals.com/content/8/4/00191-2022.full |
| spellingShingle | Jade Jaffar Mae Wong Gregory A. Fishbein Monther Alhamdoosh Laura McMillan Cristina Gamell-Fulla Milica Ng Nick Wilson Karen Symons Ian Glaspole Glen Westall Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis ERJ Open Research |
| title | Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| title_full | Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| title_fullStr | Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| title_full_unstemmed | Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| title_short | Matrix metalloproteinase-7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| title_sort | matrix metalloproteinase 7 is increased in lung bases but not apices in idiopathic pulmonary fibrosis |
| url | http://openres.ersjournals.com/content/8/4/00191-2022.full |
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