Cited by 507Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisProtease and Inhibitor MechanismsPulmonary Hypertension Research and Treatments

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Matrix Metalloproteinases as Therapeutic Targets for Idiopathic Pulmonary Fibrosis

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Craig, Vanessa J., Zhang, Li, Hagood, James S., Owen, Caroline A.·2015·American Journal of Respiratory Cell and Molecular Biology

DOI 10.1165/rcmb.2015-0020trPMC PMC4742954

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a restrictive lung disease that is associated with high morbidity and mortality. Current medical therapies are not fully effective at limiting mortality in patients with IPF, and new therapies are urgently needed. Matrix metalloproteinases (MMPs) are proteinases that, together, can degrade all components of the extracellular matrix and numerous nonmatrix proteins. MMPs and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the pathogenesis of IPF based upon the results of clinical studies reporting elevated levels of MMPs (including MMP-1, MMP-7, MMP-8, and MMP-9) in IPF blood and/or lung samples. Surprisingly, studies of gene-targeted mice in murine models of pulmonary fibrosis (PF) have demonstrated that most MMPs promote (rather than inhibit) the development of PF and have identified diverse mechanisms involved. These mechanisms include MMPs: (1) promoting epithelial-to-mesenchymal transition (MMP-3 and MMP-7); (2) increasing lung levels or activity of profibrotic mediators or reducing lung levels of antifibrotic mediators (MMP-3, MMP-7, and MMP-8); (3) promoting abnormal epithelial cell migration and other aberrant repair processes (MMP-3 and MMP-9); (4) inducing the switching of lung macrophage phenotypes from M1 to M2 types (MMP-10 and MMP-28); and (5) promoting fibrocyte migration (MMP-8). Two MMPs, MMP-13 and MMP-19, have antifibrotic activities in murine models of PF, and two MMPs, MMP-1 and MMP-10, have the potential to limit fibrotic responses to injury. Herein, we review what is known about the contributions of MMPs and TIMPs to the pathogenesis of IPF and discuss their potential as therapeutic targets for IPF.

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Additional file 8 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
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Additional file 10 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576190
Additional file 3 of MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts
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Additional file 7 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986305
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Additional file 4 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986281
Additional file 3 of Therapeutic efficacy of thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles on Escherichia coli-induced acute lung injury in mice
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Additional file 2 of MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts
Zhang, Y., Mo, Y., Zhang, Y., Yuan, J., & Zhang, Q. (2024) · Figshare · doi:10.6084/m9.figshare.26590853
Additional file 5 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986290
Additional file 1 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576199
Additional file 3 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576205
Additional file 7 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576217
Additional file 1 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986254
Additional file 4 of MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts
Zhang, Y., Mo, Y., Zhang, Y., Yuan, J., & Zhang, Q. (2024) · Figshare · doi:10.6084/m9.figshare.26590859
Additional file 1 of Associations of MMP9 polymorphism with the risk of severe pneumonia in a Southern Chinese children population
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Additional file 6 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576214
Additional file 2 of Associations of MMP9 polymorphism with the risk of severe pneumonia in a Southern Chinese children population
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Additional file 8 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576220
Additional file 11 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576193
Additional file 2 of Therapeutic efficacy of thrombin-preconditioned mesenchymal stromal cell-derived extracellular vesicles on Escherichia coli-induced acute lung injury in mice
Bang, Y., Hwang, S., Kim, Y. E., Sung, D. K., Yang, M., Ahn, S. Y., Sung, S. I., Joo, K. M., & Chang, Y. S. (2024) · Figshare · doi:10.6084/m9.figshare.26517916
Additional file 2 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576202
Additional file 3 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986272
Additional file 5 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576211
Additional file 2 of Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Todd, J. L., Vinisko, R., Liu, Y., Neely, M. L., Overton, R. A., Flaherty, K. R., Noth, I., Newby, L. K., Lasky, J. A., Olman, M. A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.11986263
Additional file 12 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
Liu, C. X., Fan, H., Ma, J., Ma, L., & Ge, R.-L. (2021) · Figshare · doi:10.6084/m9.figshare.16576196
Additional file 1 of MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts
Zhang, Y., Mo, Y., Zhang, Y., Yuan, J., & Zhang, Q. (2024) · Figshare · doi:10.6084/m9.figshare.26590850
Additional file 6 of MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts
Zhang, Y., Mo, Y., Zhang, Y., Yuan, J., & Zhang, Q. (2024) · Figshare · doi:10.6084/m9.figshare.26590865
Additional file 9 of In vitro and in vivo efficacy of thiacloprid against Echinococcus multilocularis
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Authors: Craig, V. J., Zhang, L., Hagood, J. S., & Owen, C. A.
Affiliations: Brigham and Women's Hospital (US)
University of California San Diego (US)
Corresponding author: Owen, Caroline A.
ORCID: Hagood, James S.
Owen, Caroline A.
Venue: American Journal of Respiratory Cell and Molecular Biology
Publisher: Oxford University Press (OUP)
Published: 2015-11-01
Volume: 53
Issue: 5
Pages: 585-600
ISSN: 1044-1549 (ISSN-L)
1535-4989
DOI: 10.1165/rcmb.2015-0020tr
PMC: PMC4742954
OpenAlex: W1676246072
Cited by: 507
References: 210
Citations by year: 2026: 43 · 2025: 49 · 2024: 60 · 2023: 60 · 2022: 56 · 2021: 60 · 2020: 60 · 2019: 49 · 2018: 28 · 2017: 25 · 2016: 13 · 2015: 3
FWCI: 18.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Brigham and Women's Hospital
U.S. Public Health Service (CIA123046)
National Heart, Lung, and Blood Institute (HL114501, HL105339, R01HL086814, P01HL105339, AI111475-01, HL086814, R21HL111835, HL111835, HL063137, R01HL063137, T32HL007633, P01HL114501)
National Institute of Allergy and Infectious Diseases (R01AI111475, AI111475‐01)
National Institute of Environmental Health Sciences (P30ES007033)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
Keywords: idiopathic pulmonary fibrosis, matrix metalloproteinases, tissue inhibitors of metalloproteinases, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, MMP-19, epithelial-mesenchymal transition, macrophage polarization, extracellular matrix degradation, therapeutic target, antifibrotic mechanism
MeSH terms: Animals, Cell Movement, Disease Models, Animal, Extracellular Matrix, Gene Expression Regulation, Humans, Lung, Signal Transduction, Randomized Controlled Trials as Topic, Macrophages, Alveolar, Mice, Matrix Metalloproteinases, Secreted, Idiopathic Pulmonary Fibrosis, Epithelial-Mesenchymal Transition, Molecular Targeted Therapy, Matrix Metalloproteinase Inhibitors

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Matrix Metalloproteinases as Therapeutic Targets for Idiopathic Pulmonary Fibrosis

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