Liu Yan, Gu Fangle, Gao Jun, Gu Yingyan, Li Zhiyue, Lu Dan, Zhang Yanxin
Department of Obstetrics and Gynecology, Clinical Medical College, Yangzhou University, No. 98 Nantong West Road, Yangzhou, 225001, China.
Cell Div. 2024 May 11;19(1):18. doi: 10.1186/s13008-024-00118-w.
The precise mechanisms underlying preeclampsia (PE) pathogenesis remain unclear. Mesenchymal stem cells (MSCs) are involved in the pathology of PE. The aim of our study was to identify the effects of protein phosphatase 2 regulatory subunit B α (PPP2R2A) on MSCs and ascertain its latent role in the progression of PE.
Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the expression of PPP2R2A in decidual tissue and decidual (d)MSCs from healthy pregnant women and patients with PE as well as the expression levels of Bax and Bcl-2 in dMSCs. The levels of p-PI3K, PI3K, p-AKT, and AKT were determined using western blotting. Cell growth, apoptosis, and migration were analyzed using MTT, flow cytometry, and Transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation ability was assayed using a HUVEC capillary-like tube formation assay.
PPP2R2A was downregulated in decidual tissues and dMSCs of patients with PE when compared with that in healthy pregnant women. Moreover, upregulation of PPP2R2A enhanced cell proliferation, reduced apoptotic dMSC, inhibited Bax expression, and increased Bcl-2 levels. Conditioned medium from PPP2R2A-overexpressing dMSCs promoted HTR-8/SVneo cell migration and angiogenesis of HUVEC. Furthermore, the PPP2R2A plasmid suppressed PI3K/AKT pathway activation in dMSCs. However, these effects were partially reversed by LY2940002 treatment.
PPP2R2A inhibition contributes to PE by regulating the proliferation, apoptosis, and angiogenesis of MSCs, providing a new therapeutic target for PE diagnosis and treatment.
子痫前期（PE）发病机制的确切机制仍不清楚。间充质干细胞（MSCs）参与了PE的病理过程。我们研究的目的是确定蛋白磷酸酶2调节亚基Bα（PPP2R2A）对MSCs的影响，并确定其在PE进展中的潜在作用。
采用逆转录定量聚合酶链反应和蛋白质印迹分析，以确定PPP2R2A在健康孕妇和PE患者的蜕膜组织及蜕膜间充质干细胞（dMSCs）中的表达，以及dMSCs中Bax和Bcl-2的表达水平。采用蛋白质印迹法测定p-PI3K、PI3K、p-AKT和AKT的水平。分别采用MTT法、流式细胞术和Transwell实验分析细胞生长、凋亡和迁移情况。采用人脐静脉内皮细胞（HUVEC）毛细血管样管形成实验检测HUVEC的管形成能力。
与健康孕妇相比，PE患者的蜕膜组织和dMSCs中PPP2R2A表达下调。此外，PPP2R2A的上调增强了细胞增殖，减少了dMSCs的凋亡，抑制了Bax表达，并增加了Bcl-2水平。过表达PPP2R2A的dMSCs的条件培养基促进了HTR-8/SVneo细胞迁移和HUVEC的血管生成。此外，PPP2R2A质粒抑制了dMSCs中PI3K/AKT信号通路的激活。然而，LY2940002处理部分逆转了这些作用。
PPP2R2A抑制通过调节MSCs的增殖、凋亡和血管生成导致PE，为PE的诊断和治疗提供了新的治疗靶点。
