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PMID: 1918385 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta.

The Journal of clinical investigation ·Vol. 88 ·No. 4 ·1991-10-00 ·Pages 1346-53

Sawdey MS, Loskutoff DJ

Abstract

The regulation of type 1 plasminogen activator inhibitor (PAI-1) gene expression was studied in vivo employing a murine model system. Nuclease protection analysis revealed relatively high concentrations of PAI-1 mRNA in the aorta, adipose tissue, heart, and lungs of untreated CB6 (BalbC X C57B16) mice. Treatment of CB6 mice with LPS, TNF-alpha, or transforming growth factor-beta (TGF-beta) increased the steady-state levels of PAI-1 mRNA within 3 h in all tissues examined. However, the greatest responses to TGF-beta were observed in adipose tissue and the kidney, while LPS and TNF-alpha strongly stimulated PAI-1 gene expression in the liver, kidney, lung, and adrenals. In C3H/HeJ mice, which exhibit defective TNF-alpha release in response to LPS, the response of the PAI-1 gene to LPS was severely attenuated. However, injection of these mice with TNF-alpha increased PAI-1 mRNA in a tissue-specific pattern strikingly similar to that observed in LPS-treated CB6 mice. These results demonstrate that the PAI-1 gene is regulated in a complex and tissue-specific manner in vivo, and suggest a role for TNF-alpha in the response of the PAI-1 gene to sepsis.

MeSH Terms
Adipose Tissue/metabolism Animals Dose-Response Relationship, Drug Gene Expression Regulation/drug effects Lipopolysaccharides Liver/metabolism Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Organ Specificity Plasminogen Inactivators RNA, Messenger/analysis Transforming Growth Factor beta/pharmacology Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Lipopolysaccharides Plasminogen Inactivators RNA, Messenger Transforming Growth Factor beta Tumor Necrosis Factor-alpha
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sawdey M S
Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Loskutoff D J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI115440
Published
1991-10-00
Pages
1346-53
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295605
Subset
IM
Grants
NHLBI NIH HHS · HL-16411 · United States
NHLBI NIH HHS · HL-22289 · United States
NIAID NIH HHS · T32 AI-07244 · United States
External Links
PubMed source DOI: 10.1172/JCI115440 PMC Full Text View journal details
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