Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia
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 activati...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5574 |
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| author | Agata Sakowicz Michalina Bralewska Tadeusz Pietrucha Dominika E Habrowska-Górczyńska Agnieszka W Piastowska-Ciesielska Agnieszka Gach Magda Rybak-Krzyszkowska Piotr J Witas Hubert Huras Mariusz Grzesiak Lidia Biesiada |
| author_facet | Agata Sakowicz Michalina Bralewska Tadeusz Pietrucha Dominika E Habrowska-Górczyńska Agnieszka W Piastowska-Ciesielska Agnieszka Gach Magda Rybak-Krzyszkowska Piotr J Witas Hubert Huras Mariusz Grzesiak Lidia Biesiada |
| author_sort | Agata Sakowicz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:59:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:59:06Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-14e75f755949445bb6e1602383bf22a82023-11-20T09:01:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012115557410.3390/ijms21155574Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in PreeclampsiaAgata Sakowicz0Michalina Bralewska1Tadeusz Pietrucha2Dominika E Habrowska-Górczyńska3Agnieszka W Piastowska-Ciesielska4Agnieszka Gach5Magda Rybak-Krzyszkowska6Piotr J Witas7Hubert Huras8Mariusz Grzesiak9Lidia Biesiada10Medical University of Lodz, Department of Medical Biotechnology, 90-752 Lodz, PolandMedical University of Lodz, Department of Medical Biotechnology, 90-752 Lodz, PolandMedical University of Lodz, Department of Medical Biotechnology, 90-752 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, 90-752 Lodz, PolandMedical University of Lodz, Department of Cell Cultures and Genomic Analysis, 90-752 Lodz, PolandDepartment of Genetics, Polish Mother’s Memorial Hospital-Research Institute in Lodz, 93-338 Lodz, PolandDepartment of Obstetrics and Perinatology, University Hospital in Krakow, 31-501 Krakow, PolandMedical University of Lodz, Department of Haemostatic Disorders, 92-215 Lodz, PolandDepartment of Obstetrics and Perinatology, University Hospital in Krakow, 31-501 Krakow, PolandDepartment of Perinatology, Obstetrics and Gynecology, Polish Mother’s Memorial Hospital-Research Institute in Lodz, 93-338 Lodz, PolandDepartment of Obstetrics and Gynecology, Polish Mother’s Memorial Hospital-Research Institute, 93-338 Lodz, PolandAlthough 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.https://www.mdpi.com/1422-0067/21/15/5574canonical activation pathwaygene expressionnon-canonical activation pathwayNuclear Factor kBplacentapreeclampsia |
| spellingShingle | Agata Sakowicz Michalina Bralewska Tadeusz Pietrucha Dominika E Habrowska-Górczyńska Agnieszka W Piastowska-Ciesielska Agnieszka Gach Magda Rybak-Krzyszkowska Piotr J Witas Hubert Huras Mariusz Grzesiak Lidia Biesiada Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia International Journal of Molecular Sciences canonical activation pathway gene expression non-canonical activation pathway Nuclear Factor kB placenta preeclampsia |
| title | Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia |
| title_full | Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia |
| title_fullStr | Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia |
| title_full_unstemmed | Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia |
| title_short | Canonical, Non-Canonical and Atypical Pathways of Nuclear Factor кb Activation in Preeclampsia |
| title_sort | canonical non canonical and atypical pathways of nuclear factor кb activation in preeclampsia |
| topic | canonical activation pathway gene expression non-canonical activation pathway Nuclear Factor kB placenta preeclampsia |
| url | https://www.mdpi.com/1422-0067/21/15/5574 |
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