Department of Surgery, University of Michigan, Ann Arbor, USA.
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, USA.
Inflammation. 2023 Apr;46(2):491-508. doi: 10.1007/s10753-022-01769-z. Epub 2023 Jan 4.
Hypoxia-inducible factors (HIFs) are transcription factors critical for the adaptive response to hypoxia. There is also an essential link between hypoxia and inflammation, and HIFs have been implicated in the dysregulated immune response to various insults. Despite the prevalence of hypoxia in tissue trauma, especially involving the lungs, there remains a dearth of studies investigating the role of HIFs in clinically relevant injury models. Here, we summarize the effects of HIF-1α on the vasculature, metabolism, inflammation, and apoptosis in the lungs and review the role of HIFs in direct lung injuries, including lung contusion, acid aspiration, pneumonia, and COVID-19. We present data that implicates HIF-1α in the context of arguments both in favor and against its role as adaptive or injurious in the propagation of the acute inflammatory response in lung injuries. Finally, we discuss the potential for pharmacological modulation of HIFs as a new class of therapeutics in the modern intensive care unit.
缺氧诱导因子 (HIFs) 是对缺氧适应反应至关重要的转录因子。缺氧与炎症之间也存在着重要的联系，HIFs 已被牵涉到各种损伤的免疫反应失调中。尽管组织创伤，特别是肺部创伤中存在缺氧，但仍缺乏研究 HIFs 在临床相关损伤模型中的作用。在这里，我们总结了 HIF-1α 对肺部血管、代谢、炎症和细胞凋亡的影响，并回顾了 HIFs 在直接肺损伤中的作用，包括肺挫伤、酸吸入、肺炎和 COVID-19。我们提供的数据表明，HIF-1α 在支持和反对其在肺损伤中急性炎症反应的适应性或损伤性传播中的作用的争论中都有牵连。最后，我们讨论了将 HIFs 作为一种新型治疗方法用于现代重症监护病房的潜在可能性。
