help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on October 23, 2009
Am. J. Respir. Cell Mol. Biol. 2009, doi:10.1165/rcmb.2009-0046OC
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Shetty, S.
Right arrow Articles by Idell, S.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shetty, S.
Right arrow Articles by Idell, S.

Submitted on February 3, 2009
Accepted on October 23, 2009

Posttranscriptional Regulation of Plasminogen Activator Inhibitor-1 Expression in Human Pleural Mesothelial Cells

Sreerama Shetty1*, Thirunavukkarasu Velusamy1, Rashmi S Shetty1, Amarnath Satheesh Marudamuthu1, Shwetha K Shetty1, Galina Florova1, Torry Tucker1, Kathy Koenig1, Praveenkumar Shetty1, Yashodhar P Bhandary1, and Steven Idell1

1 The Texas Lung Injury Institute, The University of Texas Health Center at Tyler, Tyler, Texas, United States

* To whom correspondence should be addressed. E-mail: sreerama.shetty{at}uthct.edu.

The plasminogen activator inhibitor (PAI-1) effectively blocks the activities of both free and receptor bound urokinase-type plasminogen activator (uPA). Incubation of cultured human pleural mesothelial (Met5A) cells with TGF-{beta} increased PAI-1 protein. TGF-{beta}{beta}-globin mRNA, indicating that the binding sequence accelerates decay of endogenous PAI-1 mRNA. Competitive inhibition by overexpression of the 33 nt binding sequence in MeT5A cells reduced PAI-1 mRNA decay and increased PAI-1 protein and mRNA expression, indicating that the PAI-1 mRNABp destabilizes PAI-1 mRNA by its interaction with the endogenous 33 nt binding sequence. Incubation of Met5A cells with TGF-{beta} attenuated the interaction of the PAI-1 mRNABp with the 33 nt sequence. By conventional and affinity purification, we isolated the PAI-1 mRNABp and confirmed its identity as 6-Phospho-D-Gluconate-NADP oxidoreductase (6-PGD). 6-PGD specifically interacts with the full length as well as the 33 nt sequence of the PAI-1 mRNA 3'UTR. This newly recognized pathway could influence expression of PAI-1 by mesothelial or mesothelioma cells at the level of mRNA stability in the context of pleural inflammation or malignancy.
Key words: pleural • mesothelial cells • plasminogen activator • Fibrinolysis






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2009 American Thoracic Society. 		  Red In Translatin