Higgins Debra F, Kimura Kuniko, Iwano Masayuki, Haase Volker H
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Cell Cycle. 2008 May 1;7(9):1128-32. doi: 10.4161/cc.7.9.5804. Epub 2008 Feb 11.
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.
毛细血管稀疏是纤维化疾病的一个标志，会导致血液灌注和氧气输送减少。在肾脏中，肾小管间质纤维化会导致肾组织破坏和肾功能不可逆转的丧失，这与缺氧和缺氧诱导因子（HIF）信号通路的激活有关。HIF-1和HIF-2是碱性螺旋-环-螺旋转录因子，它们通过调节能量代谢、血管重塑、红细胞生成、细胞增殖和凋亡，使细胞能够在低氧环境中存活。最近的研究表明，HIF激活会促进上皮-间质转化（EMT）和肾纤维化。这些发现增加了一种可能性，即在急性和慢性缺氧条件下，HIF激活的对缺氧应激的生物学反应谱可能不同。在这里，我们讨论HIF信号通路在慢性肾脏病发病机制和进展中的作用。
