PMID- 26121236
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20220408
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 53
IP  - 5
DP  - 2015 Nov
TI  - Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary 
      fibrosis.
PG  - 585-600
LID - 10.1165/rcmb.2015-0020TR [doi]
AB  - 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.
FAU - Craig, Vanessa J
AU  - Craig VJ
AD  - 1 Division of Pulmonary and Critical Care Medicine, Brigham and Women's 
      Hospital/Harvard Medical School, Boston, Massachusetts.
AD  - 2 Division of Pulmonary, Critical Care, and Sleep Medicine, University of 
      California-San Diego, La Jolla, California.
FAU - Zhang, Li
AU  - Zhang L
AD  - 1 Division of Pulmonary and Critical Care Medicine, Brigham and Women's 
      Hospital/Harvard Medical School, Boston, Massachusetts.
FAU - Hagood, James S
AU  - Hagood JS
AD  - 3 Division of Pediatric Respiratory Medicine, University of California-San Diego, 
      La Jolla, California, and.
AD  - 4 Rady Children's Hospital of San Diego, San Diego, California; and.
FAU - Owen, Caroline A
AU  - Owen CA
AD  - 1 Division of Pulmonary and Critical Care Medicine, Brigham and Women's 
      Hospital/Harvard Medical School, Boston, Massachusetts.
AD  - 5 Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
LA  - eng
GR  - HL086814/HL/NHLBI NIH HHS/United States
GR  - T32 HL007633/HL/NHLBI NIH HHS/United States
GR  - HL111835/HL/NHLBI NIH HHS/United States
GR  - HL063137/HL/NHLBI NIH HHS/United States
GR  - HL105339/HL/NHLBI NIH HHS/United States
GR  - CIA123046/PHS HHS/United States
GR  - P01 HL105339/HL/NHLBI NIH HHS/United States
GR  - R01 AI111475/AI/NIAID NIH HHS/United States
GR  - R01 HL063137/HL/NHLBI NIH HHS/United States
GR  - HL114501/HL/NHLBI NIH HHS/United States
GR  - R21 HL111835/HL/NHLBI NIH HHS/United States
GR  - AI111475-01/AI/NIAID NIH HHS/United States
GR  - R01 HL086814/HL/NHLBI NIH HHS/United States
GR  - P01 HL114501/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Secreted)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Disease Models, Animal
MH  - Epithelial-Mesenchymal Transition/drug effects/genetics
MH  - Extracellular Matrix/drug effects/pathology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*drug therapy/enzymology/*genetics/pathology
MH  - Lung/*drug effects/enzymology/pathology
MH  - Macrophages, Alveolar/*drug effects/enzymology/pathology
MH  - Matrix Metalloproteinase Inhibitors/therapeutic use
MH  - Matrix Metalloproteinases, Secreted/antagonists & 
      inhibitors/classification/*genetics/metabolism
MH  - Mice
MH  - Molecular Targeted Therapy
MH  - Randomized Controlled Trials as Topic
MH  - Signal Transduction
PMC - PMC4742954
OTO - NOTNLM
OT  - fibrosis
OT  - idiopathic pulmonary fibrosis
OT  - interstitial lung disease
OT  - lung
OT  - matrix metalloproteinase
EDAT- 2015/06/30 06:00
MHDA- 2016/02/03 06:00
PMCR- 2016/11/01
CRDT- 2015/06/30 06:00
PHST- 2015/06/30 06:00 [entrez]
PHST- 2015/06/30 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2015-0020TR [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2015 Nov;53(5):585-600. doi: 10.1165/rcmb.2015-0020TR.