Klekamp J G, Jarzecka K, Hoover R L, Summar M L, Redmond N, Perkett E A
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2586, USA.
Pediatr Res. 1997 Dec;42(6):744-9. doi: 10.1203/00006450-199712000-00005.
Chronic lung disease in neonates results from both lung injury and inadequate repair processes. Little is known about the growth factors involved in lung injury and repair, but vascular endothelial growth factor (VEGF) has recently been reported in several animal models of lung injury. VEGF is an endothelial cell-specific mitogen, which is also known as vascular permeability factor because of its ability to induce vascular leak in some tissues. Chronic lung disease is complicated by increased vascular permeability, which can be improved by avoidance of hypoxia and in some cases by dexamethasone therapy. In many cells, hypoxia stimulates VEGF expression. Also, in some cases, dexamethasone blocks VEGF expression. This study examined the role of hypoxia and dexamethasone in regulating the expression of VEGF in pulmonary artery smooth muscle cells. An ovine VEGF cDNA fragment (453 bp) was cloned and found to be highly homologous to known human sequences for VEGF165. Sheep pulmonary artery smooth muscle cells were cultured and exposed to room air, hypoxia, and dexamethasone, alone or in combination for 6 h. At baseline these cells expressed VEGF mRNA at approximately 3.9 kb. The half-life of VEGF mRNA in the smooth muscle cells was 171 min, more than 3-fold longer than previous reports for epithelial cells. Exposure to hypoxia caused a 3-fold increase in mRNA abundance, primarily through transcriptional up-regulation. Dexamethasone blocked the hypoxia-induced increase in VEGF mRNA. The results demonstrate that hypoxia and dexamethasone are regulators of VEGF expression in ovine pulmonary artery smooth muscle cells. It is not known whether VEGF derived from these cells is involved in lung injury and/or normal homeostatsis.
新生儿慢性肺部疾病是由肺损伤和修复过程不足共同导致的。关于参与肺损伤和修复的生长因子，人们了解甚少，但最近在几种肺损伤动物模型中报道了血管内皮生长因子（VEGF）。VEGF是一种内皮细胞特异性促有丝分裂原，因其在某些组织中诱导血管渗漏的能力，也被称为血管通透性因子。慢性肺部疾病会因血管通透性增加而复杂化，避免缺氧以及在某些情况下使用地塞米松治疗可改善这种情况。在许多细胞中，缺氧会刺激VEGF表达。此外，在某些情况下，地塞米松会阻断VEGF表达。本研究探讨了缺氧和地塞米松在调节肺动脉平滑肌细胞中VEGF表达方面的作用。克隆了一个绵羊VEGF cDNA片段（453 bp），发现它与已知的人VEGF165序列高度同源。培养绵羊肺动脉平滑肌细胞，并将其单独或联合暴露于常氧、缺氧和地塞米松环境中6小时。在基线时，这些细胞表达约3.9 kb的VEGF mRNA。VEGF mRNA在平滑肌细胞中的半衰期为171分钟，比先前报道的上皮细胞的半衰期长3倍多。暴露于缺氧环境会导致mRNA丰度增加3倍，主要是通过转录上调实现的。地塞米松阻断了缺氧诱导的VEGF mRNA增加。结果表明，缺氧和地塞米松是绵羊肺动脉平滑肌细胞中VEGF表达的调节因子。尚不清楚这些细胞产生的VEGF是否参与肺损伤和/或正常稳态。
