RESUMEN
BACKGROUND: Peroxiredoxin 1 (PRDX1), a protein with anti-inflammatory and anti-apoptotic properties, shows elevated expression in ulcerative colitis (UC). However, PRDX1's specific role in UC is poorly understood. METHODS: UC was induced in rats using dextran sulfate sodium (DSS). In vivo RNA interference was used to silence the PRDX1 expression. PRDX1 expression levels and the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, transforming growth factor (TGF)-ß and interferon (IFN)-γ in tissues were assessed by real-time quantitative polymerase chain reaction and western blotting. Colonic injury was assessed by hematoxylin-eosin staining. ELISA was used to assess levels of the inflammatory cytokines TNF-α, IL-1ß and IL-6 in colon tissues. Apoptosis of intestinal epithelial cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, and expression of the apoptotic proteins bcl-2, Bax, cleaved caspase-3 and caspase-3 was assessed by western blotting. RESULTS: PRDX1 expression was significantly increased in rats with DSS-induced UC. Silencing of PRDX1 expression improved colon injury in rats with DSS-induced UC. In addition, silencing of PRDX1 expression inhibited inflammatory responses and apoptosis of intestinal epithelial cells in rats with DSS-induced UC. CONCLUSIONS: Silencing of PRDX1 expression can ameliorate colon injury in rats with DSS-induced UC.
Asunto(s)
Colitis Ulcerosa , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/genética , Citocinas/genética , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Peroxirredoxinas/genética , Ratas , Transducción de SeñalRESUMEN
Epidermal growth factor (EGF) signaling has been shown to induce epithelial to mesenchymal transition (EMT) in many types of cancer cells. However, the molecular mechanism of EGF-induced EMT in gastric cancer remains largely unknown. In the present study, we found that human gastric cancer cell lines SGC-7901 and BGC-823 underwent EMT phenotypic changes upon exposure to EGF. The induction of EMT was consistent with aggressive characteristics such as increased cell migration, invasion and clonogenic growth. Additionally, EGF stimulation also led to the upregulation of urokinase plasminogen activator receptor (uPAR) both at mRNA and protein levels. Knockdown of uPAR by siRNA significantly attenuated EMT induction by EGF in SGC-7901 and BGC-823 cells. Furthermore, EGF increased ERK1/2 activity and blocking ERK1/2 signaling with its inhibitor, U0126, markedly inhibited EGF-induced uPAR expression and consequently EMT. Collectively, the present study demonstrated that EGF induced aggressiveness of gastric cancer cells by activating EMT, which involved the activation of the ERK1/2 pathway and, subsequently, uPAR expression.