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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.
Open accessAbstract
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.
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Cited by
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Grant, P. J. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01824.x · Cited by 443
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Hauner, H. (2005) · Proceedings of the Nutrition Society · doi:10.1079/pns2005428 · Cited by 391
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Samad, F., Yamamoto, K., Pandey, M., & Loskutoff, D. J. (1997) · Molecular Medicine · doi:10.1007/bf03401666 · Cited by 303
Self-citationShih, B., & Bayat, A. (2010) · Archives of Dermatological Research · doi:10.1007/s00403-009-1014-y · Cited by 238
Metadata
- Authors
- Sawdey, M. S., & Loskutoff, D. J.
- Venue
- Journal of Clinical Investigation
- Published
- 1991-10-01
- Volume
- 88
- Issue
- 4
- Pages
- 1346-1353
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2065699955
- Cited by
- 410
- References
- 0
- FWCI
- 9.57
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sawdey, M. S., & Loskutoff, D. J. (1991). 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. Journal of Clinical Investigation. https://doi.org/10.1172/jci115440
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