PDF(Pubmed)
Abstract：
Inflammation causes bronchopulmonary dysplasia (BPD), a common lung disease of preterm infants. One reason this disease lacks specific therapies is the paucity of information on the mechanisms regulating inflammation in developing lungs. We address this gap by characterizing the lymphatic phenotype in an experimental BPD model because lymphatics are major regulators of immune homeostasis. We hypothesized that hyperoxia (HO), a major risk factor for experimental and human BPD, disrupts lymphatic endothelial homeostasis using neonatal mice and human dermal lymphatic endothelial cells (HDLECs). Exposure to 70% O2 for 24-72 h decreased the expression of prospero homeobox 1 (Prox1) and vascular endothelial growth factor c (Vegf-c) and increased the expression of heme oxygenase 1 and NAD(P)H dehydrogenase [quinone]1 in HDLECs, and reduced their tubule formation ability. Next, we determined Prox1 and Vegf-c mRNA levels on postnatal days (P) 7 and 14 in neonatal murine lungs. The mRNA levels of these genes increased from P7 to P14, and 70% O2 exposure for 14 d (HO) attenuated this physiological increase in pro-lymphatic factors. Further, HO exposure decreased VEGFR3+ and podoplanin+ lymphatic vessel density and lymphatic function in neonatal murine lungs. Collectively, our results validate the hypothesis that HO disrupts lymphatic endothelial homeostasis.
摘要：
炎症导致支气管肺发育不良（BPD），早产儿常见的肺部疾病。这种疾病缺乏特定疗法的原因之一是缺乏有关调节肺部炎症机制的信息。我们通过在实验性BPD模型中表征淋巴表型来解决这一差距，因为淋巴管是免疫稳态的主要调节因子。我们假设高氧(HO)，实验和人类BPD的主要危险因素，使用新生小鼠和人真皮淋巴内皮细胞（HDLECs）破坏淋巴内皮稳态。暴露于70％O224-72h降低了prosprohomeobox1（Prox1）和血管内皮生长因子c（Vegf-c）的表达，并增加了血红素加氧酶1和NAD（P）H脱氢酶[醌]1的表达。HDLECs中，并降低了他们的小管形成能力。接下来,我们测定了新生儿鼠肺出生后第7天和第14天的Prox1和Vegf-cmRNA水平。这些基因的mRNA水平从P7增加到P14，并且70％O2暴露14d（HO）减弱了前淋巴因子的这种生理增加。Further,HO暴露会降低新生鼠肺的VEGFR3和足planin淋巴管密度和淋巴功能。总的来说，我们的结果验证了HO破坏淋巴管内皮稳态的假设.
