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首页> 外文期刊>American Journal of Physiology >Hypoxia-inducible factors in the kidney.
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Hypoxia-inducible factors in the kidney.

机译：肾脏缺氧诱导因子。

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摘要

Tissue hypoxia not only occurs under pathological conditions but is also an important microenvironmental factor that is critical for normal embryonic development. Hypoxia-inducible factors HIF-1 and HIF-2 are oxygen-sensitive basic helix-loop-helix transcription factors, which regulate biological processes that facilitate both oxygen delivery and cellular adaptation to oxygen deprivation. HIFs consist of an oxygen-sensitive alpha-subunit, HIF-alpha, and a constitutively expressed beta-subunit, HIF-beta, and regulate the expression of genes that are involved in energy metabolism, angiogenesis, erythropoiesis and iron metabolism, cell proliferation, apoptosis, and other biological processes. Under conditions of normal Po(2), HIF-alpha is hydroxylated and targeted for rapid proteasomal degradation by the von Hippel-Lindau (VHL) E3-ubiquitin ligase. When cells experience hypoxia, HIF-alpha is stabilized and either dimerizes with HIF-beta in the nucleus to form transcriptionally active HIF, executing the canonical hypoxia response, or it physically interacts with unrelated proteins, thereby enabling convergence of HIF oxygen sensing with other signaling pathways. In the normal, fully developed kidney, HIF-1alpha is expressed in most cell types, whereas HIF-2alpha is mainly found in renal interstitial fibroblast-like cells and endothelial cells. This review summarizes some of the most recent advances in the HIF field and discusses their relevance to renal development, normal kidney function and disease.
机译：组织缺氧不仅发生在病理条件下，而且还是重要的微环境因素，对于正常的胚胎发育至关重要。缺氧诱导因子HIF-1和HIF-2是氧敏感的基本螺旋-环-螺旋转录因子，其调节促进氧输送和细胞适应氧缺乏的生物学过程。 HIF由氧敏感性α亚基HIF-α和组成性表达的β亚基HIF-β组成，并调节参与能量代谢，血管生成，红细胞生成和铁代谢，细胞增殖，细胞凋亡和其他生物过程。在正常Po（2）的条件下，HIF-α被羟基化，并通过von Hippel-Lindau（VHL）E3-泛素连接酶靶向快速蛋白酶体降解。当细胞经历缺氧时，HIF-α稳定并与细胞核中的HIF-β二聚形成转录活性HIF，执行典型的缺氧反应，或者与不相关的蛋白质发生物理相互作用，从而使HIF氧感测与其他信号转导融合。途径。在正常，完全发育的肾脏中，HIF-1alpha在大多数细胞类型中表达，而HIF-2alpha主要在肾间质成纤维样细胞和内皮细胞中发现。这篇综述总结了HIF领域的一些最新进展，并讨论了它们与肾脏发育，正常肾脏功能和疾病的相关性。

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