Cx43 regulates mechanotransduction mechanisms in human preterm amniotic membrane defects.
Cx43 regulates mechanotransduction mechanisms in human preterm amniotic membrane defects.
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Cx43 调节人类早产羊膜缺陷的机械传导机制。
DOI：
10.1002/pd.6429
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发表时间：
2023
影响因子：
3
通讯作者：
Costa E
中科院分区：
文献类型：
--
作者：
Costa E
目的探讨机械刺激在早产羊膜(AM)缺陷中的作用。方法收集因胎儿生长受限或自发性早产前胎膜破裂(SPPROM)后急诊剖宫产(CS)患者的早产AM。用Cx43反义核酸对靠近宫颈或胎盘的AM外植体进行创伤和/或机械刺激。采用激光共聚焦显微镜、二次谐波分析、定量聚合酶链式反应和生化分析等方法，检测细胞形态、肌成纤维细胞(αSMA)、迁移(CX4 3)、炎症(PGE2)和修复(胶原、弹性蛋白和转化生长因子β[β1])等指标。机械刺激增加了胶原纤维极化，对基质标记物的影响取决于组织区域、疾病状态、胎龄和胎儿数量。在晚期sPPROM AM缺陷中，PGE2水平大致相似，但在与Cx43反义基因共治疗后PGE2水平降低。结论机械刺激对早产儿AM缺损区Cx43信号转导及细胞/胶原力学有影响。β-1和Cx43基因在创伤和机械刺激后表达明显增加，但与胎龄有关。确定Cx43如何调节机械信号传递可能是修复创伤后组织完整性的一种方法。
ObjectiveThe effects of mechanical stimulation in preterm amniotic membrane (AM) defects were explored.MethodsPreterm AM was collected from women undergoing planned preterm caesarean section (CS) due to fetal growth restriction or emergency CS after spontaneous preterm prelabour rupture of the membranes (sPPROM). AM explants near the cervix or placenta were subjected to trauma and/or mechanical stimulation with the Cx43 antisense. Markers for nuclear morphology (DAPI), myofibroblasts (αSMA), migration (Cx43), inflammation (PGE2) and repair (collagen, elastin and transforming growth factor β [TGFβ1]) were examined by confocal microscopy, second harmonic generation, qPCR and biochemical assays.ResultsIn preterm AM defects, myofibroblast nuclei were highly deformed and contractile and expressed αSMA and Cx43. Mechanical stimulation increased collagen fibre polarisation and the effects on matrix markers were dependent on tissue region, disease state, gestational age and the number of fetuses. PGE2levels were broadly similar but reduced after co‐treatment with Cx43 antisense in late sPPROM AM defects. TGFβ1and Cx43 gene expression were significantly increased after trauma and mechanical stimulation but this response dependent on gestational age.ConclusionMechanical stimulation affects Cx43 signalling and cell/collagen mechanics in preterm AM defects. Establishing how Cx43 regulates mechanosignalling could be an approach to repair tissue integrity after trauma.