Disease relevance of STAT3

• To define the molecular mechanisms involved, the effect of peroxynitrite was determined on the activation of two transcription factors known to regulate VEGF expression during hypoxia and tumor angiogenesis-signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1 (HIF-1) [1].
• CONCLUSIONS: The present study showed that STAT3 is expressed and activated in kidneys of rats with modified immune complex glomerulonephritis [2].
• IL-6 signaling is activated during human chronic atrophic gastritis with Helicobacter pylori infection, and aberrant Stat3 signaling activation gives rise to mouse gastric tumors [3].

High impact information on STAT3

• These results indicate that shear flow induces the phosphorylation of Ser-727 via ERK1/2 pathway, and this Ser-727 phosphorylation inhibits Tyr-705 phosphorylation in STAT3 [4].
• Shear flow attenuates serum-induced STAT3 activation in endothelial cells [4].
• Recent studies indicate that STAT3 is involved in growth factor-induced cell cycle [4].
• Moreover, transduction of endothelial cells with dominant-negative STAT3 abrogated the peroxynitrite-induced increase in VEGF mRNA [1].
• Peroxynitrite caused activation and nuclear translocation of STAT3, but not HIF-1 [1].

Chemical compound and disease context of STAT3

• Expression and activation of STAT3 in chronic proliferative immune complex glomerulonephritis and the effect of fosinopril [2].

Biological context of STAT3

• Bovine aortic ECs cultured with serum at static state show a serum concentration-dependent phosphorylation at Tyr-705 of STAT3, whereas there is a constant basal phosphorylation at Ser-727 [4].
• In conclusion, leptin improved the ability of the oocyte to sustain embryonic development and had long-term effects on blastocyst apoptosis and transcript abundance of LEPR, STAT3, and apoptosis-associated genes [5].
• In summary, we demonstrate for the first time that resveratrol inhibits IL-6-induced ICAM-1 gene expression, in part, by interfering with Rac-mediated pathways via the attenuation of STAT3 phosphorylation [6].

Anatomical context of STAT3

• Peroxynitrite increases VEGF expression in vascular endothelial cells via STAT3 [1].
• Following BK stimulation of BAECs, however, the B2R and STAT3 are translocated out of caveolae [7].
• STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (Review) [3].
• STAT3-induced Wnt5a activates non-canonical Wnt signaling in rat cardiac myocytes for N-cadherin-dependent aggregation [3].

Associations of STAT3 with chemical compounds

• BK also activates the mitogen-activated p44 and p42 protein kinases, resulting in STAT3 serine phosphorylation [7].
• Activation results in the tyrosine phosphorylation and subsequent nuclear translocation of STAT3 [7].
• LPS-responsive regions of the promoter were localized to the region from -1029 to -543 containing one STAT3 site and two NF-kappaB sites, and the region from -4355 to -2462 containing three AP1 sites and six NF-kappaB sites [8].
• Finally, fosinopril downregulated STAT3 activation and ED-1 influx, which are effects that may attenuate renal damage in this model [2].
• Conversely, exposure of ECs to a NOS inhibitor reversed the effects of resveratrol upon IL-6-induced STAT3 phosphorylation [6].

Enzymatic interactions of STAT3

• In contrast, nuclear levels of STAT-1 and phosphorylated STAT-3 were elevated in a time-dependent manner in response to IFNgamma treatment [9].

Other interactions of STAT3

• Resveratrol suppresses IL-6-induced ICAM-1 gene expression in endothelial cells: effects on the inhibition of STAT3 phosphorylation [6].

Analytical, diagnostic and therapeutic context of STAT3

• Analysis of immunohistochemistry showed that STAT3 and p-STAT3 were expressed in very few cells of normal rats, that expression was strong in model rats and that this increased expression was attenuated in the fosinopril group (P<0.05) [2].
• The expression and activation of STAT3 and the expression of TIMP-1, one of the STAT3 downstream genes, were observed in renal tissues of rats by means of immunohistochemistry, electrophoretic mobility shift assay (EMSA), western blot and northern blot [2].

References