Placental dysferlin expression is reduced in severe preeclampsia.
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.
Lang
C T
CT
Department of Obstetrics & Gynecology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Markham
K B
KB
Behrendt
N J
NJ
Suarez
A A
AA
Samuels
P
P
Vandre
D D
DD
Robinson
J M
JM
Ackerman
W E
WE
D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014327:Trophoblasts / Q000378:metabolism; D055815:Young Adult
D002135:Calcium-Binding Proteins; C114839:DYSF protein, human; D000073939:Dysferlin; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger