Matrix Biol. 2018 Mar 5. pii: S0945-053X(17)30471-7. doi: 10.1016/j.matbio.2018.03.001. [Epub ahead of print]
The impaired proteases and anti-proteases balance in Idiopathic Pulmonary Fibrosis.
Idiopathic Pulmonary Fibrosis
(IPF) is a devastating chronic, progressive and irreversible disease
that remains refractory to current therapies.
Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the development of pulmonary fibrosis since decades. Coagulation signalling deregulation, which influences several key inflammatory and fibro-proliferative responses, is also essential in IPF pathogenesis, and a growing body of evidence indicates that Protease-Activated Receptors (PARs) inhibition in IPF may be promising for future evaluation.
Therefore, proteases and anti-proteases aroused great biomedical interest over the past years, owing to the identification of their potential roles in lung fibrosis. During these last decades, numerous other proteases and anti-proteases have been studied in lung fibrosis, such as matriptase, Human airway trypsin-like protease (HAT), Hepatocyte growth factor activator (HGFA)/HGFA activator inhibitor (HAI) system, Plasminogen activator inhibitor (PAI)-1, Protease nexine (PN)-1, cathepsins, calpains, and cystatin C.
Herein, we provide a general overview of the proteases and anti-proteases unbalance during lung fibrogenesis and explore potential therapeutics for IPF.
Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of MMPs (TIMPs), have been implicated in the development of pulmonary fibrosis since decades. Coagulation signalling deregulation, which influences several key inflammatory and fibro-proliferative responses, is also essential in IPF pathogenesis, and a growing body of evidence indicates that Protease-Activated Receptors (PARs) inhibition in IPF may be promising for future evaluation.
Therefore, proteases and anti-proteases aroused great biomedical interest over the past years, owing to the identification of their potential roles in lung fibrosis. During these last decades, numerous other proteases and anti-proteases have been studied in lung fibrosis, such as matriptase, Human airway trypsin-like protease (HAT), Hepatocyte growth factor activator (HGFA)/HGFA activator inhibitor (HAI) system, Plasminogen activator inhibitor (PAI)-1, Protease nexine (PN)-1, cathepsins, calpains, and cystatin C.
Herein, we provide a general overview of the proteases and anti-proteases unbalance during lung fibrogenesis and explore potential therapeutics for IPF.
KEYWORDS:
Anti-protease; Cysteine protease; Idiopathic Pulmonary Fibrosis; Matrix metalloproteinase; Serine protease- PMID:
- 29518524
- DOI:
- 10.1016/j.matbio.2018.03.001
Outline
- Highlights
- Abstract
- Keywords
- Idiopathic Pulmonary Fibrosis (IPF)
- Pro- and anti-fibrotic lung proteases and anti-proteases deregulation in IPF
- Matrix metalloproteinases (MMPs) and their cognate inhibitors
- MMPs
- TIMPs
- Cysteine proteases and their cognate inhibitors
- Cysteine proteases cathepsins, ATG4B, and calpains
- Cystatin C
- Serine proteases and their cognate inhibitors
- Coagulation serine proteases
- Type II transmembrane serine proteases (TTSPs)
- The HGFA-HAI imbalance in IPF
- Serine proteases inhibitors: plasminogen activator inhibitor-1 (PAI-1) and protease nexin-1 (PN-1) serpins
- Matrix metalloproteinases (MMPs) and their cognate inhibitors
- Therapeutic targeting of proteases/anti-proteases for IPF
- Future directions
- Conflicts of interest
- Funding sources
- References
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