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首页> 外文期刊>American Journal of Physiology >Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth.
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Regulated expression of hypoxia-inducible factors during postnatal and postpneumonectomy lung growth.

机译：出生后和肺切除术后肺生长过程中缺氧诱导因子的调控表达。

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We previously found increased expression of erythropoietin receptor (EPO-R) in peripheral dog lung during postnatal and postpneumonectomy (PNX) lung growth. To study the upstream regulation of EPO-R, we analyzed the expression of hypoxia-inducible factors (HIF)-1alpha, -2alpha, and -3alpha during postnatal lung growth in immature and mature (2.5 and 12 mo old, respectively) dogs and during compensatory lung growth 3 wk and 10 mo after right PNX. Relative to their respective controls, HIF-1alpha transcript was 52-95% higher in immature lungs and 284% higher in the remaining lung 3 wk post-PNX. HIF-2alpha transcript did not change during maturation but was 42% lower 3 wk post-PNX. HIF-3alpha transcript was 53-65% lower in both the immature lung and 3 wk post-PNX. Changes were no longer detectable 10 mo post-PNX. No change in HIF transcripts was observed in kidney and liver post-PNX. Consistent with the mRNA changes, HIF-1alpha protein was 120 and 196% higher in growing lungs and 3 wk post-PNX relative totheir respective controls. Overexpression of HIF-1alpha in cultured HEK-293 cells increased endogenous expression of EPO-R protein. These results demonstrate regulated expression of the HIF system and parallel changes in HIF-1alpha and EPO-R expression during two types of lung growth. Because the normal growing lung is not hypoxic, the HIF system likely responds to other signals encountered during sustained lung strain.
机译：我们先前发现在产后和肺切除术后（PNX）肺生长期间，外周血狗肺中促红细胞生成素受体（EPO-R）的表达增加。为了研究EPO-R的上游调节，我们分析了低氧诱导因子（HIF）-1alpha，-2alpha和-3alpha在未成熟和成熟（分别为2.5和12个月大）的狗和右PNX后3 wk和10 mo进行代偿性肺生长期间。相对于它们各自的对照，未成熟肺中HIF-1alpha转录物高出52-95％，而在PNX后3周，其余肺中HIF-1alpha转录物高出284％。 HIF-2alpha转录物在成熟期间没有变化，但在PNX后3周降低了42％。在未成熟肺和PNX后3周时，HIF-3alpha转录物均降低53-65％。 PNX后10个月不再检测到更改。 PNX后在肾脏和肝脏中未观察到HIF转录物的变化。与mRNA的变化一致，相对于它们各自的对照，生长中的肺和PNX后3周的HIF-1α蛋白分别高120和196％。在培养的HEK-293细胞中HIF-1alpha的过表达增加了EPO-R蛋白的内源性表达。这些结果表明，在两种类型的肺部生长过程中，HIF系统的表达受到调控，HIF-1alpha和EPO-R表达平行变化。因为正常的肺生长不是低氧的，所以HIF系统可能会对持续的肺劳损期间遇到的其他信号作出反应。

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