间充质干细胞
微泡
医学
抗磷脂综合征
脐带
胎盘
免疫学
炎症
肿瘤坏死因子α
细胞凋亡
癌症研究
滋养层
抗体
怀孕
胎儿
病理
小RNA
生物
生物化学
遗传学
基因
作者
Qingfeng Li,Yuan Wang,Tian Wang,Yuqiu Liu,Mengqi Gu,Xiaotong Jiang,Yao Cai,Ran Huo,Yuchen Li,Lei Li,Xietong Wang
标识
DOI:10.1186/s12951-023-02179-5
摘要
Abstract Exosomes originating from human umbilical cord mesenchymal stem cells (hucMSC-exos) have become a novel strategy for treating various diseases owing to their ability to regulate intercellular signal communication. However, the potential of hucMSC-exos to improve placental injury in obstetric antiphospholipid syndrome and its underlying mechanism remain unclear. Our objective was to explore the potential application of hucMSC-exos in the treatment of obstetric antiphospholipid syndrome and elucidate its underlying mechanism. In our study, hucMSC-exos ameliorated the functional impairment of trophoblasts caused by antiphospholipid antibodies in vitro and attenuated placental dysfunction in mice with obstetric antiphospholipid syndrome by delivering miR-146a-5p. Exosomal miR-146a-5p suppressed the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibited the activation of NF-κB signaling, leading to the down-regulation of IL-1β and IL-18 to rescue inflammation and modulation of Cleaved-CASP3, BAX, and BCL2 to inhibit apoptosis in HTR8/SVneo cells and mice placenta. This study identified the potential molecular basis of how hucMSC-exos improved antiphospholipid antibody-induced placental injury and highlighted the functional importance of the miR-146a-5p/TRAF6 axis in the progression of obstetric antiphospholipid syndrome. More importantly, this study provided a fresh outlook on the promising use of hucMSC-exos as a novel and effective treatment approach in obstetric antiphospholipid syndrome. Graphical Abstract
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