Nitric oxide serves various roles in mammalian cells, including intracellular 
signaling and cell killing. To recognize the dynamic molecular changes in 
response to NO, microarray analysis was applied to human fibroblasts (IMR-90) 
exposed to sublethal levels of NO. Among the > 300 transcripts induced by NO, we 
focused on the mRNA encoded by the transforming growth factor-beta- (TGF-beta-) 
inducible early response 1 gene (TIEG1), which plays a pivotal role in 
TGF-beta-regulated cell growth control and apoptosis. Northern blotting analysis 
demonstrated that NO upregulates TIEG1 mRNA in a dose-dependent manner. 
Anti-TGF-beta antibodies prevented TIEG1 mRNA induction by TGF-beta, but not the 
induction by NO. Conversely, NO had no effect on the amounts of total TGF-beta 
or its active form in culture supernatants. However, the half-life of the TIEG1 
transcript was strongly increased (6-fold) upon exposure of the cells to NO. 
Thus, NO upregulates TIEG1 mRNA by stabilization independently of TGF-beta. The 
TIEG1 mRNA now joins heme oxygenase-1 mRNA in displaying regulation by 
NO-mediated stabilization. It remains to be determined whether the same control 
mechanism operates on these and perhaps other messages.