TY - JOUR
T1 - Decreased intracellular iron availability suppresses epithelial cell surface plasmin generation
T2 - Transcriptional and post-transcriptional effects on u-PA and PAI-1 expression
AU - Hasegawa, Takashi
AU - Sorensen, Lise
AU - Ooi, Hidemi
AU - Marshall, Bruce C.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1165/ajrcmb.21.2.3445
DO - 10.1165/ajrcmb.21.2.3445
M3 - Article
C2 - 10423412
AN - SCOPUS:0033174283
VL - 21
SP - 275
EP - 282
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 2
ER -