Diabetic retinopathy is manifested by excessive angiogenesis and high level of vascular endothelial growth factor (VEGF) in the eye. Human (MIO-M1) and rat (rMC-1) Müller cells were treated with 0, 5. Show more
Diabetic retinopathy is manifested by excessive angiogenesis and high level of vascular endothelial growth factor (VEGF) in the eye. Human (MIO-M1) and rat (rMC-1) Müller cells were treated with 0, 5.5, or 30mM glucose for 24 hours. Viable cell counts were obtained by Trypan Blue Dye Exclusion Method. ELISA was used to determine VEGF levels in cell medium. Compared to 24 hour treatment by 5.5mM glucose, MIO-M1 and rMC-1 in 30mM glucose increased in viable cell number by 38% and 24% respectively. In contrast, viable cells in 0mM glucose decreased by 28% and 50% respectively. Compared to 5.5mM, MIO-M1 and rMC-1 in 30mM glucose had increased levels of VEGF in cell medium (pg/ml by 24% and 20%) and also VEGF concentration in cells held in 0mM increased by 47% and 10% respectively. In both MIO-M1 and rMC-1, the amount of VEGF secreted per cell increased by about 100% when glucose was changed from 5.5 to 0mM but decreased slightly (17% in MIO-M1 and 11% in rMC-1) when glucose was increased from 5.5 to 30mM. Our results show that MIO-M1 and rMC-1 are highly responsive to changes in glucose concentrations. 30mM compared to 5.5mM significantly increased cell viability but induced a significant change in VEGF secretion per cell in rMC-1 only. At 0, 5.5, and 30mM glucose, MIO-M1 secreted about 5-7-fold higher level of VEGF (pg/cell) than rMC-1. The mechanism of glucose-induced changes in rMC-1 and MIO-M1 cell viability and VEGF secretion remains to be elucidated. Show less
Many types of human cancers having hyperactivated Wnt signaling display no causative alterations in known effectors of this pathway. Here, we report a function of TGIF in Wnt signaling. TGIF associate Show more
Many types of human cancers having hyperactivated Wnt signaling display no causative alterations in known effectors of this pathway. Here, we report a function of TGIF in Wnt signaling. TGIF associates with and diverts Axin1 and Axin2 from the β-catenin destruction complex, therefore allowing β-catenin accrual. Intriguingly, activation of Wnt signaling induces the expression of TGIF, which unveils a feed-forward loop that ensures effective integration of Wnt signaling. In triple-negative breast cancers (TNBC), elevated levels of TGIF correlate with high Wnt signaling and poor survival of patients. Moreover, genetic experiments revealed that Tgif1 ablation impeded mammary tumor development in MMTV-Wnt1 mice, further underscoring a requirement of TGIF for oncogenic Wnt signaling. Show less