帮忙修改以下英文Hypoxia is a signature of tumor microenvironment and it promotes tumor progression by stabilizing transcription factor HIF1α 21 We therefore examined whether hypoxia affects the role of TGFβ i

Hypoxia is a distinct characteristic of the tumor microenvironment, and it promotes tumor progression by stabilizing the transcription factor HIF1α. We investigated whether hypoxia affects the ability of TGFβ to suppress angiogenesis and found that when tumor-bearing mice were treated with PX-478, a HIF1α inhibitor, Hepa-TGFβ-derived xenografts showed a significant decrease in both microvessel area and density. However, tumor growth was not affected by TGFβ overexpression or HIF1α inhibition, which may be due to the rapid growth of xenografts and the short experiment period. We then treated Tg(fli1:EGFP) transgenic zebrafish embryos with DMOG, which mimics hypoxia exposure, and found that DMOG exposure significantly abolished the effect of TGFβ in reducing the SIV area. These in vivo results suggest that hypoxia may weaken the anti-angiogenic function of TGFβ in tumors.

Further in vitro capillary tube formation assays, using HUVEC and HBMEC, revealed that TGFβ treatment significantly inhibited EC from forming capillary-like structures in a dose-dependent manner, which mirrored the anti-angiogenic effect of TGFβ in zebrafishes. TGFβ treatment also significantly repressed EC migration but did not affect EC proliferation. In line with the in vivo observations, incubation under hypoxic conditions or treatment with DMOG could abolish the roles of TGFβ in inhibiting EC migration and tube formation. These hypoxia-induced effects were reversed by silencing HIF1α in EC. These findings suggest that hypoxia may negate the anti-angiogenic function of TGFβ via HIF1α in EC.

Overall, our results indicate that TGFβ may inhibit physiological angiogenesis under normoxia conditions, but its anti-angiogenic effect may be weakened under hypoxia conditions, such as in the tumor microenvironment