Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia.

Int J Mol Sci 2020 Aug 4;21(15). Epub 2020 Aug 4.

Department of Obstetrics and Gynecology, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.

Although higher nuclear factor κB (NFκB) expression and activity is observed in preeclamptic placentas, its mechanism of activation is unknown. This is the first study to investigate whether the canonical, non-canonical, or atypical NFκB activation pathways may be responsible for the higher activation of NFκB observed in preeclamptic placentas. The study included 268 cases (130 preeclamptic women and 138 controls). We studied the expression of the genes coding for NFκB activators (NIK, IKKα, IKKβ, and CK2α) and inhibitors (IκBα and IκBβ) using RT-PCR in real time. The RT-PCR results were verified on the protein level using ELISA and Western blot. To determine the efficiency of the pathways, the ratios of activator(s) to one of the inhibitors (IκBα or IκBβ) were calculated for each studied pathway. The preeclamptic placentas demonstrated significantly lower IKKα and CK2α but higher IκBα and IκBβ protein levels. In addition, the calculated activator(s) to inhibitor (IκBα or IκBβ) ratios suggested that all studied pathways might be downregulated in preeclamptic placentas. Our results indicate that preeclamptic placentas may demonstrate mechanisms of NFκB activation other than the canonical, non-canonical, and atypical forms. In these mechanisms, inhibitors of NFκB may play a key role. These observations broaden the existing knowledge regarding the molecular background of preeclampsia development.

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21155574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432517PMC
August 2020

Publication Analysis

Top Keywords

preeclamptic placentas
20
iκbα iκbβ
16
canonical non-canonical
12
non-canonical atypical
12
nfκb activation
8
nuclear factor
8
inhibitors iκbα
8
observed preeclamptic
8
nfκb
6
preeclamptic
6
placentas
5
activation
5
ck2α inhibitors
4
ikkβ ck2α
4
iκbα
4
ratios suggested
4
iκbβ
4
iκbβ rt-pcr
4
iκbβ ratios
4
rt-pcr real
4

Similar Publications