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miR-125b Enhances IL-8 Production in Early-Onset Severe Preeclampsia by Targeting Sphingosine-1-Phosphate Lyase 1
Weiwei Yang1,2, Anning Wang3, Chunling Zhao1,2
1School of Biological Sciences, Weifang Medical University, Weifang, China.
Insights
MicroRNA-125b (miR-125b) is linked to preeclampsia (PE) development. This study reveals miR-125b promotes inflammation by targeting SGPL1, increasing IL-8 levels, a key factor in PE pathogenesis.
Area of Science:
- Reproductive biology
- Molecular medicine
- Inflammation research
Background:
- Preeclampsia (PE) is a major cause of maternal and perinatal mortality.
- Impaired inflammation is a hallmark of preeclampsia.
- The role of specific microRNAs in PE pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of microRNA-125b (miR-125b) in preeclampsia.
- To identify the molecular targets and pathways regulated by miR-125b in PE.
- To explore the association between miR-125b, SGPL1, and IL-8 in PE.
Main Methods:
- Analysis of miR-125b and SGPL1 expression in placental tissues and plasma from PE patients.
- Luciferase assays to confirm SGPL1 as a direct target of miR-125b.
- Assessment of IL-8 production in response to miR-125b and SGPL1 manipulation.
Main Results:
- miR-125b was deregulated in PE patients' placental tissues and plasma.
- miR-125b directly targets and downregulates sphingosine-1-phosphate lyase 1 (SGPL1) expression.
- miR-125b enhances IL-8 production, which was reversed by SGPL1 overexpression; increased IL-8 was observed in PE patients.
Conclusions:
- miR-125b plays a critical role in regulating IL-8 production.
- The miR-125b/SGPL1/IL-8 axis is implicated in the pathogenesis of preeclampsia.
- Targeting miR-125b may offer a therapeutic strategy for preeclampsia.
Abstract:
Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. One of the main hallmarks observed in PE is impaired inflammation state. In the current study, we found that miR-125b was deregulated in placental tissues and plasma derived from PE patients, which suggest a potential association between this miRNA and the pathogenesis of PE. Overexpression of miR-125b significantly reduced SGPL1 expression, and luciferase assays confirmed that SGPL1 is a direct target of miR-125b. We also found that miR-125b enhanced IL-8 production by directly targeting sphingosine-1-phosphate lyase 1 (SGPL1), and this effect could be reversed by SGPL1 overexpression. In placentas derived from PE patients, a negative correlation of miR-125b and SGPL1 was observed, and IL-8 was validated to be increased in the circulation of PE patients. Our data demonstrated a critical role of miR-125b in IL-8 production and the development of PE.
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