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PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model.
Biochem Biophys Res Commun. 2002 Jun 28; 294(5):1155-60.BB

Abstract

Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-1(-/-) and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after OVA challenge compared with saline challenge. However, in PAI-1(-/-) mice, collagen deposition was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold higher. This is the first direct evidence that the plasmin system regulates ECM deposition in the airways of a murine asthma model, independently of the effect of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM deposition occurs.

Authors+Show Affiliations

Division of Allergy and Immunology, Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, School of Medicine, University of California, Bldg. N25, 1000 W. Carson St., Los Angeles, Torrance, CA 90509, USA. coh@rei.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12074598

Citation

Oh, Chad K., et al. "PAI-1 Promotes Extracellular Matrix Deposition in the Airways of a Murine Asthma Model." Biochemical and Biophysical Research Communications, vol. 294, no. 5, 2002, pp. 1155-60.
Oh CK, Ariue B, Alban RF, et al. PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model. Biochem Biophys Res Commun. 2002;294(5):1155-60.
Oh, C. K., Ariue, B., Alban, R. F., Shaw, B., & Cho, S. H. (2002). PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model. Biochemical and Biophysical Research Communications, 294(5), 1155-60.
Oh CK, et al. PAI-1 Promotes Extracellular Matrix Deposition in the Airways of a Murine Asthma Model. Biochem Biophys Res Commun. 2002 Jun 28;294(5):1155-60. PubMed PMID: 12074598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model. AU - Oh,Chad K, AU - Ariue,Barbara, AU - Alban,Rodrigo F, AU - Shaw,Bryan, AU - Cho,Seong H, PY - 2002/6/21/pubmed PY - 2002/7/31/medline PY - 2002/6/21/entrez SP - 1155 EP - 60 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 294 IS - 5 N2 - Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-1(-/-) and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after OVA challenge compared with saline challenge. However, in PAI-1(-/-) mice, collagen deposition was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold higher. This is the first direct evidence that the plasmin system regulates ECM deposition in the airways of a murine asthma model, independently of the effect of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM deposition occurs. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/12074598/PAI_1_promotes_extracellular_matrix_deposition_in_the_airways_of_a_murine_asthma_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(02)00577-6 DB - PRIME DP - Unbound Medicine ER -