School of Pediatrics, Nanjing Medical University, Nanjing, Jiangsu, China; Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.
Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.
Int J Biochem Cell Biol. 2023 Oct;163:106464. doi: 10.1016/j.biocel.2023.106464. Epub 2023 Sep 1.
In the NICU, bronchopulmonary dysplasia (BPD) is a concerning common respiratory complication in preterm and low birth-weight infants. Clinical studies have confirmed that human milk has an important nutritional role for children with BPD, therefore, dentification of beneficial components in human milk that prevent BPD is urgently needed. Our previous work showed that human milk exosomes (HM-Exos) could inhibit apoptosis of alveolar type II epithelial cells (AT II), and the circular RNA (circRNA)-circABPD1 were highly expressed in preterm colostrum milk exosomes. Exosomes transport circRNAs that are stable and may exert anti-inflammatory and immune effects attracted the attention of researchers, but the role and mechanism of human milk exosome-derived circABPD1 in BPD remains unclear. Here, we constructed BPD in vivo and in vitro models through exposure to hyperoxia, verified the effect of circABPD1 and revealed its mechanism through rescue experiments. We found that circABPD1 had circRNA properties, and overexpression of circABPD1 could improve reduced alveolar number, enlarged the alveolar linear intercept in vivo models of BPD, promote cell proliferation, reduce oxidative stress levels and alleviate lung epithelial cell damage in vivo and in vitro models. Mechanistically, circABPD1 targets miR-330-3p and regulates the expression of HIF1α. These results suggest that circABPD1 can improve the pathologoical changes of bronchopulmonary dysplasia, promote cell proliferation, inhibit oxidative stress level, and alleviate lung injury by targeting the miR-330-3p/HIF1α axis, which provides a new idea for the prevention and treatment of bronchopulmonary dysplasia.
在新生儿重症监护病房（NICU）中，支气管肺发育不良（BPD）是早产儿和低出生体重儿常见的令人担忧的呼吸系统并发症。临床研究已经证实，人乳对患有 BPD 的儿童具有重要的营养作用，因此，迫切需要确定人乳中预防 BPD 的有益成分。我们之前的工作表明，人乳外泌体（HM-Exos）可以抑制肺泡 II 型上皮细胞（AT II）的凋亡，并且 circABPD1 在早产儿初乳外泌体中高表达。外泌体运输稳定的 circRNAs，可能发挥抗炎和免疫作用，引起了研究人员的关注，但人乳外泌体衍生的 circABPD1 在 BPD 中的作用和机制尚不清楚。在这里，我们通过暴露于高氧来构建体内和体外 BPD 模型，通过挽救实验验证了 circABPD1 的作用并揭示了其机制。我们发现 circABPD1 具有 circRNA 特性，circABPD1 的过表达可以改善 BPD 体内模型中肺泡数量减少和肺泡线性截距增大的情况，促进细胞增殖，降低氧化应激水平并减轻体内和体外模型中的肺上皮细胞损伤。从机制上讲，circABPD1 靶向 miR-330-3p 并调节 HIF1α 的表达。这些结果表明，circABPD1 可以通过靶向 miR-330-3p/HIF1α 轴改善支气管肺发育不良的病理变化，促进细胞增殖，抑制氧化应激水平，减轻肺损伤，为支气管肺发育不良的防治提供了新的思路。
