氧感应机制在发育和组织修复中的作用。
Oxygen-sensing mechanisms in development and tissue repair.
机构信息
Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
出版信息
Development. 2021 Dec 1;148(23). doi: 10.1242/dev.200030. Epub 2021 Dec 7.
Abstract
Under normoxia, hypoxia inducible factor (HIF) α subunits are hydroxylated by PHDs (prolyl hydroxylase domain proteins) and subsequently undergo polyubiquitylation and degradation. Normal embryogenesis occurs under hypoxia, which suppresses PHD activities and allows HIFα to stabilize and regulate development. In this Primer, we explain molecular mechanisms of the oxygen-sensing pathway, summarize HIF-regulated downstream events, discuss loss-of-function phenotypes primarily in mouse development, and highlight clinical relevance to angiogenesis and tissue repair.
摘要
在常氧条件下，缺氧诱导因子（HIF）α亚基被 PHD（脯氨酰羟化酶结构域蛋白）羟化，随后发生多泛素化和降解。在缺氧条件下，正常的胚胎发生会发生，这会抑制 PHD 活性，使 HIFα稳定并调节发育。在这篇概述中，我们解释了氧感应途径的分子机制，总结了 HIF 调节的下游事件，讨论了主要在小鼠发育中丧失功能表型，并强调了其与血管生成和组织修复的临床相关性。
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