Differential expressions and roles of hypoxia-inducible factor-1α, -2α and -3α in the rat carotid body during chronic and intermittent hypoxia
Differential expressions and roles of hypoxia-inducible factor-1α, -2α and -3α in the rat carotid body during chronic and intermittent hypoxia
复制标题
DOI：
10.14670/hh-23.271
复制
发表时间：
2008-03-01
影响因子：
2
通讯作者：
Fung, Man-Lung
中科院分区：
文献类型：
--
作者：
Lam, Siu-Yin;Tipoe, George L.;Fung, Man-Lung
HIF-1 α在颈动脉体（CB）中的表达是慢性缺氧（CH）中CB结构和功能变化的转录调节的中心。CB在睡眠呼吸障碍患者的心血管发病率中起致病作用;然而，HIF-α亚型在间歇性缺氧（IH）中的表达和作用，类似于复发性发作性呼吸暂停，尚不清楚。我们假设不同的作用，HIF-α亚型，调节CB响应IH的差异表达。CB体积和HIF-1 α、HIF-2 α、HIF-3 α和HIF调节的基因产物（包括血管内皮生长因子（VEGF）、内皮素-1（ET-1）和酪氨酸羟化酶（TH））的表达谱的时程分析显示，在IH期间大鼠CB体积、HIF-1 α和VEGF表达缺乏增加方面存在显著差异，尽管CH组中HIF-1 α mRNA水平增加，体积和表达显著增加。与此相反，在IH和CH组中，CB中HIF-2 α和HIF-3 α的表达以及ET-1和TH的表达均增加。结果表明HIF-2 α和HIF-3 α在CB对IH的反应中发挥了重要作用，这可能与低氧条件下HIF-1 α的表达和作用互补。HIF-α亚型和通路的这种差异调节可以解释CB对IH和CH反应的形态学和神经化学差异。
The HIF-1 alpha expression in the carotid body (CB) is central to the transcriptional regulation of the CB structural and functional changes in chronic hypoxia (CH). The CB plays pathogenic roles in cardiovascular morbidity in patients with sleep-disordered breathing; yet, the expression and role of HIF-alpha subtypes in intermittent hypoxia (IH), resembling recurrent episodic apnea, are unclear. We hypothesized a divergent role of HIF-alpha subtypes, regulated by differential expression in the CB response to IH. A time-course analysis of the CB volume, and expression profiles of the HIF-1 alpha, -2 alpha, -3 alpha and HIF-regulated gene products, including vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and tyrosine hydroxylase (TH), showed a significant difference in the lack of increase in the rat CB volume, HIF-1 alpha and VEGF expression during IH, despite an increase in the mRNA level of HIF-1 alpha and the prominent increase of volume and expression in the CH group. In contrast, there were increased CB expressions of HIF-2 alpha and -3 alpha, and also ET-1 and TH in both IH and CH groups. Results demonstrated a significant role played by HIF-2 alpha and -3 alpha in the CB response to IH, which could be complementary to the expression and role of HIF-1 alpha under hypoxic conditions. This differential regulation of the HIF-alpha subtypes and pathways could account for the morphological and neurochemical discrepancy in the CB responses to IH and CH.