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

First Author  Emert MP Year  1998
Journal  Am J Physiol Volume  274
Issue  2 Pt 2 Pages  F405-12
PubMed ID  9486236 Mgi Jnum  J:92928
Mgi Id  MGI:3055039 Doi  10.1152/ajprenal.1998.274.2.F405
Citation  Emert MP, et al. (1998) The human plasminogen activator inhibitor type I gene promoter targets to kidney. Am J Physiol 274(2 Pt 2):F405-12
abstractText  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-beta (TGF-beta). 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-beta 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-beta in the experimental protocol used.
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