Sufentanil alleviates pre-eclampsia via silencing microRNA-24-3p to target 11β-Hydroxysteroid dehydrogenase type 2

Abstract

Pre-eclampsia (PE) is a prevalent pregnancy disease characterized by insufficient trophoblast cell migration (HTR8/SVneo). Consequently, accelerating trophoblast cell proliferation might ameliorate PE. This study assessed the effects and molecular mechanisms of Sufentanil (SUF) on HTR8/SVneo cells proliferation. HTR8/SVneo cells and PE clinical samples were used. Peripheral blood was collected from PE patients’ samples, and microRNA (miR)-24-3p and 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) was analyzed in the blood and cells. HTR8/SVneo cells were treated with varying SUF concentrations or transfected with miR-24-3p mimics/inhibitors, or HSD11B2 elevation vector. CCK-8, colony formation, transwell, and flow cytometry assays were then carried out. Association of miR-24 − 3p with HSD11B2 was investigated. PE animal model was constructed using Wistar rats to verify SUF’s role on PE in vivo . According to the results, SUF boosted HTR8/SVneo cell proliferation, and inhibited miR-24-3p to accelerate HSD11B2. MiR-24-3p was increased in PE, while HSD11B2 was inhibited, and miR-24-3p targeted HSD11B2. HSD11B2 reversed miR-24-3p’s repression on HTR/SVneo cell advancement. SUF restrained PE’s progression in vivo and in vitro via mediating the miR-24-3p/HSD11B2 axis. In conclusion, SUF enhances HSD11B2 via repressing miR-24-3p, thereby suppressing PE’s progression. The study provides an insight into the possibility of using SUF as a novel therapeutic target for PE, which acts via combining with miR-24-3p.

Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development

“…Future targets for analysis might include proteins confirmed to have a positive [p38 Mitogen-activated protein kinases (MAPK)], or negative [extracellular signal-regulated kinase (ERK)1/2 MAPK], effect on the regulation of placental 11 β -HSD2 [ 85 ]. Medications known to alter DNA methylation or histone modifications as well as non-coding RNAs (e.g., miR-24-3p) may also provide indirect changes in the regulation of 11 β -HSD2 [ 86 , 87 ], highlighting another area for future studies. Future studies should also link placental biomarkers to higher-order deficits and secondary disabilities in children with PAE (e.g., executive functioning, impulsivity, metabolic disorder, obesity) and examine the sensitivity and specificity of placenta and cord blood biomarkers with respect to these long-term outcomes.…”

MicroRNAs: key regulators of the trophoblast function in pregnancy disorders

“…This review summarized miRNAs that target corresponding mRNAs and regulate the biological function of trophoblasts in pregnancy disorders, including trophoblast cell invasion, proliferation, migration, differentiation, apoptosis, autophagy, pyroptosis, ferroptosis, cellular metabolism, and angiogenesis through different pathways. Proper function of the trophoblast is essential for embryonic development, while the abnormal function of the trophoblast may lead to pregnancy disorders [ 190 , 191 ]. Of note, pyroptosis and ferroptosis are the most studied programmed cell death modes in recent years, but few studies have investigated the regulation of miRNAs in pregnancy disorders by regulating pyroptosis and ferroptosis of trophoblast cells.…”

“…It is interesting to note that the differential expression of lncRNA and circRNA is closely related to the occurrence and development of pregnancy disorders [ 190 , 191 , 194 ]. For example, so far, lncRNA H19 (H19) is one of the most thoroughly studied lncRNAs [ 195 ], and H19 is closely related to the occurrence and development of PE and IUGR [ 192 , 196 , 197 ].…”

“…For example, so far, lncRNA H19 (H19) is one of the most thoroughly studied lncRNAs [ 195 ], and H19 is closely related to the occurrence and development of PE and IUGR [ 192 , 196 , 197 ]. Compared with normal pregnant women, patients with early RSA have 123 differentially expressed circRNAs, of which 78 are up-regulated and 45 are down-regulated, but the specific mechanism remains unclear [ 191 ]. Therefore, the differential expression of lncRNAs and circRNAs in pregnancy diseases may be a focus for future pregnancy disorders research.…”