纤连蛋白家族蛋白在人胎膜宫颈旁薄弱区及其他区域的差异表达。
Differential expression of fibulin family proteins in the para-cervical weak zone and other areas of human fetal membranes.
作者信息
Moore R M, Redline R W, Kumar D, Mercer B M, Mansour J M, Yohannes E, Novak J B, Chance M R, Moore J J
机构信息
Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
出版信息
Placenta. 2009 Apr;30(4):335-41. doi: 10.1016/j.placenta.2009.01.007. Epub 2009 Feb 23.
OBJECTIVE
Human fetal membranes (FM) at term have been shown to contain a weak zone in the region overlying the cervix which exhibits characteristics of increased collagen remodeling and apoptosis. It has been hypothesized that the FM rupture initiation site is within this weak zone. Although the FM weak zone has been partially characterized, it is unclear what structural differences in the extracellular matrix result in its decreased rupture strength. A screen for differentially expressed proteins in the amnion of the weak zone versus other FM areas demonstrated that fibulin 1 was decreased. We investigated potential regional differences in all fibulin protein family members.
METHODS
FM fibulins were localized by immunohistochemistry. Detected fibulins were screened by Western blot for differences in abundance in the amnion of the weak zone versus non-weak zone FM regions. Amnion epithelial and mesenchymal cells were also screened for fibulin production.
RESULTS
Fibulins 1 and 5 were detected in the cytoplasm of and in a pericellular pattern surrounding all FM cells, and in a dense extracellular pattern in the amniotic compact zone. Fibulin 3 was detected within the cytoplasm of amnion epithelial and chorion trophoblast cells. Fibulins 2 and 4 were not detected. Fibulins 1, 3 and 5 demonstrated decreased abundance of 33%, 63% and 58% (all P<0.01) in amnion of the weak zone relative to other FM regions. Amnion cells produced all three detected fibulins. Furthermore, TNF inhibited amnion cell fibulin production in a dose dependent manner.
CONCLUSION
Fibulins 1, 3 and 5 were localized coincident with major microfibrillar networks in amnion. Each showed decreased abundance in the amnion component of the FM weak zone. Amnion epithelial and mesenchymal cells produced all three fibulins and their abundance was inhibited by TNF. We speculate that the amnion microfibrillar layer undergoes significant remodeling with the development of the FM weak zone.
目的
足月时的人胎膜（FM）在覆盖宫颈的区域显示出一个薄弱区，该区域表现出胶原重塑增加和细胞凋亡的特征。据推测，FM破裂起始部位就在这个薄弱区内。尽管FM薄弱区已得到部分特征描述，但尚不清楚细胞外基质中的哪些结构差异导致其破裂强度降低。对薄弱区羊膜与其他FM区域中差异表达蛋白的筛选表明，纤连蛋白1减少。我们研究了所有纤连蛋白家族成员的潜在区域差异。
方法
通过免疫组织化学对FM纤连蛋白进行定位。通过蛋白质印迹法筛选检测到的纤连蛋白在薄弱区羊膜与非薄弱区FM区域中的丰度差异。还对羊膜上皮细胞和间充质细胞的纤连蛋白产生情况进行了筛选。
结果
在所有FM细胞的细胞质中以及细胞周围模式中检测到纤连蛋白1和5，在羊膜致密区呈密集的细胞外模式。在羊膜上皮细胞和绒毛膜滋养层细胞的细胞质中检测到纤连蛋白3。未检测到纤连蛋白2和4。相对于其他FM区域，薄弱区羊膜中纤连蛋白1、3和5的丰度分别降低了33%、63%和58%（均P<0.01）。羊膜细胞产生所有三种检测到的纤连蛋白。此外，肿瘤坏死因子（TNF）以剂量依赖性方式抑制羊膜细胞纤连蛋白的产生。
结论
纤连蛋白1、3和5的定位与羊膜中的主要微原纤维网络一致。每种纤连蛋白在FM薄弱区的羊膜成分中丰度均降低。羊膜上皮细胞和间充质细胞产生所有三种纤连蛋白，且其丰度受到TNF的抑制。我们推测，随着FM薄弱区的发展，羊膜微原纤维层经历了显著的重塑。
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