Lang C T, Markham K B, Behrendt N J, Suarez A A, Samuels P, Vandre D D, Robinson J M, Ackerman W E
Department of Obstetrics & Gynecology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Placenta. 2009 Aug;30(8):711-8. doi: 10.1016/j.placenta.2009.05.008. Epub 2009 Jul 9.
Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE (n=10) and normotensive controls (n=10). DYSF and MYOF expression were examined using quantitative real-time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level (p=0.03) and 38% lower at the protein level (p=0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villi was observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE.
肌膜蛋白(DYSF)和肌成膜蛋白(MYOF)是膜蛋白ferlin家族的成员,在人胎盘合体滋养层细胞(STB)中共同表达。尽管这些ferlin蛋白在胎盘中的作用尚未明确,但有研究表明,DYSF和MYOF可能有助于顶端STB质膜的稳定性。子痫前期(PE)患者胎盘来源的细胞碎片释放增加,提示血绒毛膜界面相对不稳定。为了检测PE是否与胎盘DYSF和/或MYOF表达的改变有关,我们进行了一项横断面研究,使用从重度PE患者(n = 10)和血压正常的对照组(n = 10)收集的绒毛胎盘标本。通过定量实时RT-PCR、免疫印迹和组织标本免疫荧光标记检测DYSF和MYOF的表达。与血压正常的受试者相比,重度PE患者胎盘DYSF的mRNA水平降低了57%(p = 0.03),蛋白水平降低了38%(p = 0.026)。两组之间胎盘MYOF蛋白或mRNA表达无差异。与对照标本相比,PE患者胎盘绒毛内DYSF或MYOF的分布没有明显变化。我们得出结论,与孕周匹配的对照组相比,重度PE患者DYSF表达降低。由于DYSF在膜修复中起作用,这些数据表明DYSF在顶端STB质膜稳定性中起作用,并且可能至少部分解释了PE患者中该膜微粒脱落增加的原因。