Huc-MSC-derived exosomal miR-144 alleviates inflammation in LPS-induced preeclampsia-like pregnant rats via the FosB/ Flt-1 pathway

Background: 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. Methods: Lipopolysaccharide (LPS) was used to construct in vitro and in vivo PE -like models. Exosomes were treated with LPS-induced PE -like cells and rats. Results: PE -like inflammatory models of pregnant rats and cells were successfully constructed in vivo and in vitro. miR-144 was screened by bioinformatics analysis. Exosomes were successfully extracted. Silencing FosB, overexpressing miR-144 or treating with exosomes extracted from hucMSC overexpressing miR-144 in (Exos-MSCmiR- 144) 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-alpha (TNF-alpha), phosphorylated nuclear factor-kappaB (p-NF-kappa B)/NF-kappa B, 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-MSCmiR- 144 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-kappa B/NF-kappa B, and sFlt-1 levels. Furthermore, compared with the model group, the proportion of live births was significantly higher in the model + Exos-MSCmiR- 144 group, while the apoptosis rate of fetal rat brain tissue was significantly lower. Conclusions: 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, hucExos-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.