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Hypoxia-inducible factor signaling in the development of tissue fibrosis.

机译:缺氧诱导因子信号传导在组织纤维化的发展。

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摘要

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.
机译:毛细血管稀疏是纤维化疾病的标志,并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缺氧和缺氧诱导因子(HIF)信号的激活,从而导致肾组织破坏和肾功能不可逆转的丧失。 HIF-1和HIF-2是基本螺旋-环-螺旋转录因子,可通过调节能量代谢,血管重塑,促红细胞生成,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激活可促进上皮向间质转化(EMT)和肾纤维化。这些发现增加了在急性和慢性低氧条件下,HIF对低氧应激的生物反应谱可能不同的可能性。在这里,我们讨论了HIF信号在慢性肾脏疾病的发病机理和进展中的作用。

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