%0 Journal Article
%T WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B.
%A Zhao X
%A Su F
%A Kong F
%A Su J
%A Yang X
%A Li L
%A Li A
%A Li Q
%J Acta Cir Bras
%V 38
%N 0
%D 2023
%M 38055397
%F 1.564
%R 10.1590/acb386223
%X OBJECTIVE: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB.
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.