PDF(Pubmed)
Abstract：
Hypoxia-inducible factors (HIF) 1 and 2 regulate similar but distinct sets of target genes. Although HIFs are best known for their roles in mediating the hypoxia response accumulating evidence suggests that under certain conditions HIFs, particularly HIF2, may function also under normoxic conditions. Here we report that HIF2α functions under normoxic conditions in kidney epithelial cells to regulate formation of adherens junctions. HIF2α expression was required to induce Dock4/Rac1/Pak1-signaling mediating stability and compaction of E-cadherin at nascent adherens junctions. Impaired adherens junction formation in HIF2α- or Dock4-deficient cells led to aberrant cyst morphogenesis in 3D kidney epithelial cell cultures. Taken together, we show that HIF2α functions in normoxia to regulate epithelial morphogenesis.
摘要：
缺氧诱导因子(HIF)1和2调节相似但不同的靶基因组。尽管HIF以其在介导缺氧反应中的作用而闻名，但积累的证据表明，在某些条件下，HIF，特别是HIF2，也可以在常氧条件下发挥作用。在这里，我们报道了HIF2α在常氧条件下在肾上皮细胞中起作用以调节粘附连接的形成。HIF2α表达是诱导Dock4/Rac1/Pak1信号传导介导的稳定性和E-cadherin在新生粘附连接处的压实所必需的。HIF2α或Dock4缺陷细胞中粘附连接形成受损导致3D肾上皮细胞培养物中囊肿形态发生异常。一起来看,我们表明HIF2α在常氧中起着调节上皮形态发生的作用。
