METHODS: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model.
RESULTS: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development.
CONCLUSIONS: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.
方法:在正常胎盘和晚发型先兆子痫患者的胎盘中检测到WDR5的表达。进行CCK-8和集落形成试验以评价滋养细胞的增殖能力。通过伤口愈合和transwell测定观察迁移和侵袭。通过免疫共沉淀分析验证了WDR5与NF-κB抑制剂I-κB-α(IkBa)之间的相互作用。免疫荧光分析NF-κB的活化。最后,我们使用小鼠晚发型先兆子痫模型测试了WDR5的作用.
结果:WDR5在晚发型先兆子痫患者胎盘中高表达。WDR5过表达抑制细胞增殖,迁移,入侵滋养层。WDR5可与IkBa相互作用以激活NF-κB。NF-κB的敲低抵消了滋养细胞中WDR5过表达的抗增殖和抗转移作用。体内研究表明,靶向WDR5可以对抗迟发性先兆子痫的发展。
结论:我们的发现为WDR5在晚发型先兆子痫发展中的作用提供了新的见解。