The human plasminogen activator inhibitor type I gene promoter targets to kidney

Martin P. Emert, Christine M. Sorenson, David Basile, Joseph G. Rogers, Marc R. Hammerman, Joseph J. Billadello

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The plasminogen activator inhibitor type 1 (PAI-1) gene encodes the physiological inhibitor of tissue-type and urokinase-type plasminogen activators and is induced by cytokines such as transforming growth factor-β (TGF-β). Studies have identified DNA sequence elements within the first 1.3 kb of the 5'-upstream DNA that mediate cytokine responsiveness in transfected cells in vitro. However, the DNA sequences that mediate PAI-1 expression in vivo have not yet been delineated. To define these regulatory sequences, we generated transgenic mice that expressed a hybrid gene comprising sequences between -1,272 and +75 of the human PAI-1 gene ligated to a LacZ reporter gene. Transgene expression detected in two independent lines was observed only in kidney from embryonic day 13 to adult and was seen primarily in proximal tubule cells of the outer medulla. Transgene expression and activity were unchanged in response to TGF-β and remained restricted to kidney. Thus we have identified a promoter region within the PAI-1 gene that targets transgene expression to kidney but, unlike the native promoter, is unresponsive to TGF-β in the experimental protocol used.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume274
Issue number2 43-2
StatePublished - Feb 1998
Externally publishedYes

Fingerprint

Plasminogen Inactivators
Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Transgenes
Kidney
Genes
Cytokines
Lac Operon
Urokinase-Type Plasminogen Activator
Tissue Plasminogen Activator
Reporter Genes
Genetic Promoter Regions
Transgenic Mice
DNA

Keywords

  • Outer medulla
  • S segment
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Emert, M. P., Sorenson, C. M., Basile, D., Rogers, J. G., Hammerman, M. R., & Billadello, J. J. (1998). The human plasminogen activator inhibitor type I gene promoter targets to kidney. American Journal of Physiology - Renal Physiology, 274(2 43-2).

The human plasminogen activator inhibitor type I gene promoter targets to kidney. / Emert, Martin P.; Sorenson, Christine M.; Basile, David; Rogers, Joseph G.; Hammerman, Marc R.; Billadello, Joseph J.

In: American Journal of Physiology - Renal Physiology, Vol. 274, No. 2 43-2, 02.1998.

Research output: Contribution to journalArticle

Emert, MP, Sorenson, CM, Basile, D, Rogers, JG, Hammerman, MR & Billadello, JJ 1998, 'The human plasminogen activator inhibitor type I gene promoter targets to kidney', American Journal of Physiology - Renal Physiology, vol. 274, no. 2 43-2.
Emert, Martin P. ; Sorenson, Christine M. ; Basile, David ; Rogers, Joseph G. ; Hammerman, Marc R. ; Billadello, Joseph J. / The human plasminogen activator inhibitor type I gene promoter targets to kidney. In: American Journal of Physiology - Renal Physiology. 1998 ; Vol. 274, No. 2 43-2.
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