Placental expression of aminopeptidase-Q (laeverin) and its role in the pathophysiology of preeclampsia.
OBJECTIVE
The purpose of this study was to investigate the expression and subcellular localization of laeverin, a placenta-specific membrane-bound aminopeptidase, in preeclamptic placentas and its role in trophoblast cell migration and invasion.


STUDY DESIGN
Expression of laeverin was investigated in 6 normal and 6 preeclamptic placentas with the use of immunofluorescence, sodium dodecylsulfate-polyacrylamide gel electrophoresis with Western blot analysis and immunoelectron microscopy. The role of laeverin in trophoblast migration and invasion was studied with the use of the xCelligence system and Boyden chambers with Matrigel in HTR-8/SVneo cells. The effect of laeverin gene-silencing on selected genes that are involved in cell transformation and tumorigenesis was evaluated by polymerase chain reaction array. The Student t test, Mann-Whitney U test, χ(2) test, or F-test was used to compare groups as appropriate.


RESULTS
Laeverin was expressed in the cell membrane of villous trophoblasts in third-trimester healthy placentas; in preeclamptic placentas, it was expressed ectopically in the cytoplasm, especially in microvesicles. Immunoelectron microscopy showed laeverin leakage into the fetal capillaries and abundant expression in microvesicles in preeclamptic placentas. Migration and invasion of HTR-8/SVneo cells were reduced by 11.5% (P = .023) and 56.7% (P = .001), respectively, by laeverin gene-silencing. Analysis of downstream pathways affected by laeverin-silencing demonstrated significant down-regulation of integrin A2 (39-fold), integrin B3 (5-fold), and matrix metalloprotease 1 (36-fold).


CONCLUSION
Expression of laeverin protein is altered in preeclamptic placentas. Its ectopic expression in the cytoplasm and microvesicles, rather than the cell membrane and leakage into the fetal capillaries, may have a role in the pathophysiologic condition of preeclampsia. Laeverin gene appears to be involved in trophoblast cell migration and invasion through interaction with integrins and matrix metalloprotease 1.
['Nystad|Mona|M|', 'Sitras|Vasilis|V|', 'Larsen|Merethe|M|', 'Acharya|Ganesh|G|']
D000328:Adult D016022:Case-Control Studies D002460:Cell Line D002462:Cell Membrane D002465:Cell Movement D003593:Cytoplasm D022162:Cytoplasmic Vesicles D015536:Down-Regulation D005260:Female D055785:Gene Knockdown Techniques D006801:Humans D039421:Integrin alpha2 D039661:Integrin beta3 D020781:Matrix Metalloproteinase 1 D045726:Metalloproteases D010920:Placenta D011225:Pre-Eclampsia D011247:Pregnancy D034741:RNA, Small Interfering D020133:Reverse Transcriptase Polymerase Chain Reaction D014327:Trophoblasts
laeverin preeclampsia aminopeptidase placenta microvesicle