Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia
Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover,...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/222 |
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| author | Hsing-Fen Tsai Ching-Fen Tseng Yu-Ling Liang Pei-Ying Wu Lan-Yin Huang Yu-Han Lin Li-Hsuan Lin Chang-Ni Lin Keng-Fu Hsu |
| author_facet | Hsing-Fen Tsai Ching-Fen Tseng Yu-Ling Liang Pei-Ying Wu Lan-Yin Huang Yu-Han Lin Li-Hsuan Lin Chang-Ni Lin Keng-Fu Hsu |
| author_sort | Hsing-Fen Tsai |
| collection | DOAJ |
| description | Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (<i>p</i> < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal–fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE. |
| first_indexed | 2024-03-08T15:05:16Z |
| format | Article |
| id | doaj.art-5a4f4384124242c880891bc863c834c5 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:16Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5a4f4384124242c880891bc863c834c52024-01-10T14:58:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125122210.3390/ijms25010222Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with PreeclampsiaHsing-Fen Tsai0Ching-Fen Tseng1Yu-Ling Liang2Pei-Ying Wu3Lan-Yin Huang4Yu-Han Lin5Li-Hsuan Lin6Chang-Ni Lin7Keng-Fu Hsu8Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 70101, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Obstetrics and Gynecology, Tainan Hospital, Ministry of Health and Welfare of Taiwan, Tainan 70101, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, TaiwanPreeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (<i>p</i> < 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal–fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.https://www.mdpi.com/1422-0067/25/1/222preeclampsiaSIK3CCL24M2 skewingIL-10 |
| spellingShingle | Hsing-Fen Tsai Ching-Fen Tseng Yu-Ling Liang Pei-Ying Wu Lan-Yin Huang Yu-Han Lin Li-Hsuan Lin Chang-Ni Lin Keng-Fu Hsu Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia International Journal of Molecular Sciences preeclampsia SIK3 CCL24 M2 skewing IL-10 |
| title | Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia |
| title_full | Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia |
| title_fullStr | Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia |
| title_full_unstemmed | Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia |
| title_short | Downregulation of Salt-Inducible Kinase 3 Enhances CCL24 Activation in the Placental Environment with Preeclampsia |
| title_sort | downregulation of salt inducible kinase 3 enhances ccl24 activation in the placental environment with preeclampsia |
| topic | preeclampsia SIK3 CCL24 M2 skewing IL-10 |
| url | https://www.mdpi.com/1422-0067/25/1/222 |
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