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

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

Research output: Contribution to journalArticle

6 Scopus citations

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)
Pages (from-to)F405-F412
JournalAmerican Journal of Physiology - Renal Physiology
Volume274
Issue number2 43-2
StatePublished - Feb 1 1998
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

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  • Cite this

    Emert, M. P., Sorenson, C. M., Basile, D. P., 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), F405-F412.