PAI‐1 in tissue fibrosis

Asish K. Ghosh; Douglas E. Vaughan

doi:10.1002/jcp.22783

journal article Nov 23, 2011

PAI‐1 in tissue fibrosis

Asish K. Ghosh Douglas E. Vaughan

Journal of Cellular Physiology Vol. 227 No. 2 pp. 493-507 · Wiley

View at Publisher Save 10.1002/jcp.22783

Abstract

AbstractFibrosis is defined as a fibroproliferative or abnormal fibroblast activation‐related disease. Deregulation of wound healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the ECM depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular proteolytic activities. The urokinase/tissue type plasminogen activator (uPA/tPA) and plasmin play significant roles in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/tPA/plasmin and plasmin‐dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen activator inhibitor‐1 (PAI‐1). Under normal physiologic conditions, PAI‐1 controls the activities of uPA/tPA/plasmin/MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI‐1 inhibit uPA/tPA/plasmin and plasmin‐dependent MMP activities, and, thus, help expedite wound healing. In contrast to this scenario, under pathologic conditions, excessive PAI‐1 contributes to excessive accumulation of collagen and other ECM protein in the wound area, and thus preserves scarring. While the level of PAI‐1 is significantly elevated in fibrotic tissues, lack of PAI‐1 protects different organs from fibrosis in response to injury‐related profibrotic signals. Thus, PAI‐1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver, and skin. Paradoxically, PAI‐1 deficiency promotes spontaneous cardiac‐selective fibrosis. In this review, we discuss the significance of PAI‐1 in the pathogenesis of fibrosis in multiple organs. J. Cell. Physiol. 227: 493–507, 2012. © 2011 Wiley Periodicals, Inc.

Topics

No keywords indexed for this article. Browse by subject →

References

207

[1]

10.1152/ajplung.2001.281.3.l607

[2]

10.1152/ajplung.2001.281.3.l616

[3]

10.1152/ajplung.00378.2006

[4]

10.1128/mcb.01278-08

[5]

10.1055/s-0038-1661604

[6]

10.1160/th08-07-0427

[7]

10.1172/jci24282

[8]

10.1172/jci38369

[9]

10.1172/jci31044

[10]

10.1242/jcs.079889

[11]

10.1378/chest.99.3_supplement.81s

[12]

10.1101/gad.14.2.187

[13]

10.1074/jbc.m110.173781

[14]

10.1016/s0002-8703(03)00363-6

[15]

10.1161/01.cir.91.5.1604

[16]

10.1055/s-2004-823098

[17]

10.1016/s0168-8278(00)80123-3

[18]

10.1172/jci116892

[19]

10.1172/jci116893

[20]

10.1111/j.1755-5922.2010.00171.x

[21]

10.1016/s0002-9440(10)63015-5

[22]

10.1002/hep.23049

[23]

10.1146/annurev-physiol-012110-142225

[24]

Chen YQ "Differential mechanisms of plasminogen activator inhibitor‐1 gene activation by transforming growth factor‐beta and tumor necrosis factor‐alpha in endothelial cells" Thromb Haemost (2001) 10.1055/s-0037-1616763

[25]

Cheng X "Fosinopril and valsartan intervention in gene expression of Klotho, MMP‐9, TIMP‐1, and PAI‐1 in the kidney of spontaneously hypertensive rats" Zhong Nan Da Xue Xue Bao Yi Xue Ban (2010)

[26]

10.1016/s0002-9440(10)63674-7

[27]

10.1172/jci119815

[28]

10.4161/cc.9.22.14048

[29]

10.1002/jcp.21236

[30]

10.1016/j.coph.2005.01.007

[31]

10.1093/emboj/17.11.3091

[32]

10.1074/jbc.m413134200

[33]

Deterding RR "Prevention of bleomycin‐induced lung injury in rats by keratinocyte growth factor" Proc Assoc Am Physicians (1997)

[34]

10.1161/01.cir.0000052617.91920.fd

[35]

10.1096/fj.01-0552com

[36]

Diéval J "A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1" Blood (1991) 10.1182/blood.v77.3.528.528

[37]

10.1074/jbc.m110.174037

[38]

10.1073/pnas.062010399

[39]

10.1074/jbc.m510215200

[40]

10.1172/jci8768

[41]

10.1007/s004670000461

[42]

10.1172/jci118396

[43]

10.2174/157340810791233024

[44]

10.1046/j.1538-7836.2003.00437.x

[45]

España F "Evidence for the regulation of urokinase and tissue type plasminogen activators by the serpin, protein C inhibitor, in semen and blood plasma" Thromb Haemost (1993) 10.1055/s-0038-1649712

[46]

10.1161/01.hyp.25.4.809

[47]

10.1182/blood.v90.1.204

[48]

10.1556/aphysiol.94.2007.1-2.4

[49]

10.1073/pnas.82.24.8681

[50]

10.1016/s0168-8278(02)00272-6

Showing 50 of 207 references

Cited By

595

A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model

Enming J. Su, Pei-Suen Tsou · 2026

JCI Insight

The Potential Role of Matrix Metalloproteinase in Polycystic Ovary Syndrome: Implications for Extracellular Matrix Remodeling

Saba Nikanfar, Christiani A. Amorim · 2025

BioFactors

The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas

Fu-Shin X. Yu, Patrick S.Y. Lee · 2022

Progress in Retinal and Eye Researc...

Human amniotic mesenchymal stem cells-derived IGFBP-3, DKK-3, and DKK-1 attenuate liver fibrosis through inhibiting hepatic stellate cell activation by blocking Wnt/β-catenin signaling pathway in mice

Quan-Wen Liu, Yan-Min Ying · 2022

Stem Cell Research & Therapy

PAI-1, the Plasminogen System, and Skeletal Muscle

Fasih Ahmad Rahman, Matthew Paul Krause · 2020

International Journal of Molecular...

Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence

Douglas E. Vaughan, Rahul Rai · 2017

Arteriosclerosis, Thrombosis, and V...

Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model

Bo Yeong Jeong, Md Jamal Uddin · 2016

PLoS ONE

Genetics of chronic rhinosinusitis: State of the field and directions forward

Joy Hsu, Pedro C. Avila · 2013

Journal of Allergy and Clinical Imm...

Metrics

595

Citations

207

References

Details

Published: Nov 23, 2011
Vol/Issue: 227(2)
Pages: 493-507
License: View

Authors

Cite This Article

Asish K. Ghosh, Douglas E. Vaughan (2011). PAI‐1 in tissue fibrosis. Journal of Cellular Physiology, 227(2), 493-507. https://doi.org/10.1002/jcp.22783

PAI‐1 in tissue fibrosis

You May Also Like