Sun Jingchi, Zhang Weishe
Department of Medical Administration, The Third People's Hospital of Chengdu, Chengdu, 610014, China.
Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, 410008, China.
Heliyon. 2024 Jan 17;10(2):e24575. doi: 10.1016/j.heliyon.2024.e24575. eCollection 2024 Jan 30.
Preeclampsia (PE) is a common and severe hypertensive disorder in pregnancy. Mesenchymal stem cell-derived exosomes (Exos-MSC) have been reported to mitigate the progression of inflammatory diseases. The study aimed to explore the effects of human umbilical cord-derived Exos-MSC (huc-Exos-MSC) on PE-like models.
Lipopolysaccharide (LPS) was used to construct and PE-like models. Exosomes were treated with LPS-induced PE-like cells and rats.
PE-like inflammatory models of pregnant rats and cells were successfully constructed and . miR-144 was screened by bioinformatics analysis. Exosomes were successfully extracted. Silencing FosB, overexpressing miR-144 or treating with exosomes extracted from huc-MSC overexpressing miR-144 in (Exos-MSC) reversed the LPS-induced decline in HTR-8/SVneo cell viability and migration. In addition, the above groups decreased LPS-induced increases in interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), phosphorylated nuclear factor-kappaB (p-NF-κB)/NF-κB, soluble FMS-like tyrosine kinase 1 (sFlt-1), and Flt-1 levels. Simultaneously, transfection of miR-144 mimics and overexpressing FosB reversed those changes in the miR-144 mimics group. miR-144 might alleviate LPS-induced HTR-8/SVneo cell inflammation by targeting FosB. Injection of Exos-MSC in PE-like pregnant rats reversed LPS-induced increases in FosB expression, systolic and diastolic blood pressure (SBP and DBP), as well as mean arterial pressure (MAP), heart rate, urine albumin/creatine ratio, inflammatory factors, p-NF-κB/NF-κB, and sFlt-1 levels. Furthermore, compared with the model group, the proportion of live births was significantly higher in the model + Exos-MSC group, while the apoptosis rate of fetal rat brain tissue was significantly lower.
We found that huc-Exos-MSC-derived miR-144 alleviated gestational hypertension and inflammation in PE-like pregnant rats by regulating the FosB/Flt-1 pathway. In addition, huc-Exos-MSC-derived miR-144 could partially reverse the LPS-induced adverse pregnancy outcome and brain injury in fetal rats, laying the foundation for developing new treatments for PE.
子痫前期（PE）是妊娠期常见且严重的高血压疾病。据报道，间充质干细胞来源的外泌体（Exos-MSC）可减轻炎症性疾病的进展。本研究旨在探讨人脐带源Exos-MSC（huc-Exos-MSC）对PE样模型的影响。
使用脂多糖（LPS）构建PE样模型。将外泌体用于处理LPS诱导的PE样细胞和大鼠。
成功构建了孕鼠和细胞的PE样炎症模型。通过生物信息学分析筛选出miR-144。成功提取了外泌体。沉默FosB、过表达miR-144或用从过表达miR-144的huc-MSC中提取的外泌体（Exos-MSC）处理可逆转LPS诱导的HTR-8/SVneo细胞活力和迁移能力的下降。此外，上述各组降低了LPS诱导的白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-α）、磷酸化核因子-κB（p-NF-κB）/NF-κB、可溶性FMS样酪氨酸激酶1（sFlt-1）和Flt-1水平的升高。同时，miR-144模拟物转染和FosB过表达逆转了miR-144模拟物组的这些变化。miR-144可能通过靶向FosB减轻LPS诱导的HTR-8/SVneo细胞炎症。向PE样孕鼠注射Exos-MSC可逆转LPS诱导的FosB表达、收缩压和舒张压（SBP和DBP）以及平均动脉压（MAP）、心率、尿白蛋白/肌酐比值、炎症因子、p-NF-κB/NF-κB和sFlt-1水平的升高。此外，与模型组相比，模型+Exos-MSC组的活产比例显著更高，而胎鼠脑组织的凋亡率显著更低。
我们发现huc-Exos-MSC来源的miR-144通过调节FosB/Flt-1途径减轻PE样孕鼠的妊娠期高血压和炎症。此外，huc-Exos-MSC来源的miR-144可部分逆转LPS诱导的胎鼠不良妊娠结局和脑损伤，为开发PE的新治疗方法奠定了基础。
