Decreased intracellular iron availability suppresses epithelial cell surface plasmin generation: Transcriptional and post-transcriptional effects on u-PA and PAI-1 expression

Takashi Hasegawa, Lise Sorensen, Hidemi Ooi, Bruce C. Marshall

Research output: Contribution to journalArticlepeer-review

Abstract

Iron and iron metabolism are critical in a variety of physiologic and pathophysiologic processes, including lung injury and repair. The plasmin/plasminogen activator (PA) system is involved in the extensive remodeling process that follows acute lung injury, and alveolar epithelial cells play a key role in this repair process. Herein we report that decreased intracellular iron availability markedly suppresses cell-surface plasmin generation by A549 human carcinoma-derived pulmonary epithelial cells. This effect is mediated by concomitant downregulation of urokinase-type PA and upregulation of PA inhibitor-type I expression. Northern analyses, runoff transcription assays, and messenger RNA half-life experiments using actinomycin demonstrate that transcriptional and post-transcriptional mechanisms are operative. Given these potent in vitro effects on the plasmin/PA system, we speculate that adequate intracellular iron stores are important for successful repair of acute lung injury.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume21
Issue number2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Decreased intracellular iron availability suppresses epithelial cell surface plasmin generation: Transcriptional and post-transcriptional effects on u-PA and PAI-1 expression'. Together they form a unique fingerprint.

Cite this