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J Cell Biochem. 2018 Jan;119(1):17-27. doi: 10.1002/jcb.26146. Epub 2017 Jun 12.

Plasminogen Activator Inhibitor Type-1 as a Regulator of Fibrosis.

Author information

1
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
2
Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
3
Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran.
4
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
5
Department of Molecular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
6
Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Fibrosis is known as a frequent and irreversible pathological condition which is associated with organ failure. Tissue fibrosis is a central process in a variety of chronic progressive diseases such as diabetes, hypertension, and persistent inflammation. This state could contribute to chronic injury and the initiation of tissue repair. Fibrotic disorders represent abnormal wound healing with defective matrix turnover and clearance that lead to excessive accumulation of extracellular matrix components. A variety of identified growth factors, cytokines, and persistently activated myofibroblasts have critical roles in the pathogenesis of fibrosis. Irrespective of etiology, the transforming growth factor-β pathway is the major driver of fibrotic response. Plasminogen activator inhibitor-1 (PAI-1) is a crucial downstream target of this pathway. Transforming growth factor-β positively regulates PAI-1 gene expression via two main pathways including Smad-mediated canonical and non-canonical pathways. Overexpression of PAI-1 reduces extracellular matrix degradation via perturbing the plasminogen activation system. Indeed, elevated PAI-1 levels inhibit proteolytic activity of tissue plasminogen activator and urokinase plasminogen activator which could contribute to a variety of inflammatory elements in the injury site and to excessive matrix deposition. This review summarizes the current knowledge of critical pathways that regulate PAI-1 gene expression and suggests effective approaches for the treatment of fibrotic disease. J. Cell. Biochem. 119: 17-27, 2018.

KEYWORDS:

FIBRINOLYSIS; PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1); TISSUE PLASMINOGEN ACTIVATOR (tPA); TRANSFORMING GROWTH FACTOR-β (TGF-β); UROKINASE PLASMINOGEN ACTIVATOR (uPA)

PMID:
28520219
DOI:
10.1002/jcb.26146
[Indexed for MEDLINE]

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