Department of Neonatology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, Zhejiang, China.
Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, Zhejiang, China.
BMC Pulm Med. 2023 Jun 6;23(1):194. doi: 10.1186/s12890-023-02505-5.
Intrauterine infection/inflammation can result in fetal and neonatal lung injury. However, the biological mechanisms of intrauterine infection/inflammation on fetal and neonatal lung injury and development are poorly known. To date, there are no reliable biomarkers for improving intrauterine infection/inflammation-induced lung injury.
An animal model of intrauterine infection/inflammation-induced lung injury was established with pregnant Sprague-Dawley rats inoculated with Escherichia coli suspension. The intrauterine inflammatory status was assessed through the histological examination of the placenta and uterus. A serial of histological examinations of the fetal and neonatal rats lung tissues were performed. The fetal and neonatal rat lung tissues were harvested for next generation sequencing at embryonic day 17 and postnatal day 3, respectively. Differentially expressed mRNAs and lncRNAs were identified by conducting high-throughput sequencing technique. The target genes of identified differentially expressed lncRNAs were analyzed. Homology analyses for important differentially expressed lncRNAs were performed.
The histopathological results showed inflammatory infiltration, impaired alveolar vesicular structure, less alveolar numbers, and thickened alveolar septa in fetal and neonatal rat lung tissues. Transmission electron micrographs revealed inflammatory cellular swelling associated with diffuse alveolar damage and less surfactant-storing lamellar bodies in alveolar epithelial type II cells. As compared with the control group, there were 432 differentially expressed lncRNAs at embryonic day 17 and 125 differentially expressed lncRNAs at postnatal day 3 in the intrauterine infection group. The distribution, expression level, and function of these lncRNAs were shown in the rat genome. LncRNA TCONS_00009865, lncRNA TCONS_00030049, lncRNA TCONS_00081686, lncRNA TCONS_00091647, lncRNA TCONS_00175309, lncRNA TCONS_00255085, lncRNA TCONS_00277162, and lncRNA TCONS_00157962 may play an important role in intrauterine infection/inflammation-induced lung injury. Fifty homologous sequences in Homo sapiens were also identified.
This study provides genome-wide identification of novel lncRNAs which may serve as potential diagnostic biomarkers and therapeutic targets for intrauterine infection/inflammation-induced lung injury.
宫内感染/炎症可导致胎儿和新生儿肺损伤。然而，宫内感染/炎症对胎儿和新生儿肺损伤和发育的生物学机制尚不清楚。迄今为止，尚无改善宫内感染/炎症性肺损伤的可靠生物标志物。
采用大肠杆菌混悬液接种妊娠 Sprague-Dawley 大鼠建立宫内感染/炎症性肺损伤动物模型。通过胎盘和子宫组织学检查评估宫内炎症状态。对胎儿和新生儿大鼠肺组织进行一系列组织学检查。分别于胚胎第 17 天和出生后第 3 天采集胎儿和新生儿大鼠肺组织进行下一代测序。通过高通量测序技术鉴定差异表达的 mRNAs 和 lncRNAs。分析鉴定的差异表达 lncRNA 的靶基因。对重要差异表达 lncRNA 进行同源性分析。
组织病理学结果显示，胎儿和新生大鼠肺组织中有炎性浸润、肺泡泡状结构受损、肺泡数量减少、肺泡隔增厚。透射电镜显示，肺泡上皮 II 型细胞中弥漫性肺泡损伤伴炎症细胞肿胀，表面活性物质储存板层体减少。与对照组相比，宫内感染组在胚胎第 17 天有 432 个差异表达的 lncRNA，在出生后第 3 天有 125 个差异表达的 lncRNA。这些 lncRNA 在大鼠基因组中的分布、表达水平和功能均有显示。lncRNA TCONS_00009865、lncRNA TCONS_00030049、lncRNA TCONS_00081686、lncRNA TCONS_00091647、lncRNA TCONS_00175309、lncRNA TCONS_00255085、lncRNA TCONS_00277162 和 lncRNA TCONS_00157962 可能在宫内感染/炎症诱导的肺损伤中发挥重要作用。还鉴定了 50 个人类同源序列。
本研究提供了新型 lncRNA 的全基因组鉴定，这些 lncRNA 可能作为宫内感染/炎症性肺损伤的潜在诊断生物标志物和治疗靶点。
