Hypoxia-inducible factor signaling in the development of tissue fibrosis
Hypoxia-inducible factor signaling in the development of tissue fibrosis
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DOI：
10.4161/cc.7.9.5804
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发表时间：
2008-05-01
期刊：
影响因子：
4.3
通讯作者：
Haase, Volker H.
中科院分区：
文献类型：
--
作者：
Higgins, Debra F.;Kimura, Kuniko;Haase, Volker H.
毛细血管稀疏是纤维性疾病的标志，导致血液灌流和氧气输送减少。在肾脏中，肾小管间质纤维化与低氧和低氧诱导因子(HIF)信号的激活有关，导致肾组织的破坏和不可逆转的肾功能丧失。HIF-1和HIF-2是碱性-螺旋-环-螺旋转录因子，通过调节能量代谢、血管重塑、红细胞生成、细胞增殖和凋亡，使细胞在低氧环境中存活。最近的研究表明，HIF的激活促进了上皮向间充质转化(EMT)和肾脏纤维化的形成。这些发现提出了一种可能性，即在急性和慢性缺氧条件下，HIF激活的对低氧应激的生物反应谱可能不同。在这里，我们讨论了HIF信号在慢性肾脏疾病的发生和发展中的作用。
Capillary rarefaction is a hallmark of fibrotic diseases and results in reduced blood perfusion and oxygen delivery. In the kidney, tubulointerstitial fibrosis, which leads to the destruction of renal tissue and the irreversible loss of kidney function, is associated with hypoxia and the activation of Hypoxia-Inducible-Factor (HIF) signaling. HIF-1 and HIF-2 are basic-helix-loop-helix transcription factors that allow cells to survive in a low oxygen environment by regulating energy metabolism, vascular remodeling, erythropoiesis, cellular proliferation and apoptosis. Recent studies suggest that HIF activation promotes epithelial to mesenchymal transition (EMT) and renal fibrogenesis. These findings raise the possibility that the spectrum of HIF activated biological responses to hypoxic stress may differ under conditions of acute and chronic hypoxia. Here we discuss the role of HIF signaling in the pathogenesis and progression of chronic kidney disease.