Downregulation of lysyl oxidase and lysyl oxidase-like protein 2 suppressed the migration and invasion of trophoblasts by activating the TGF-β/collagen pathway in preeclampsia

Experimental & Molecular Medicine
Xiang-Hong XuLi-Ping Jin

Abstract

Preeclampsia is a pregnancy-specific disorder that is a major cause of maternal and fetal morbidity and mortality with a prevalence of 6-8% of pregnancies. Although impaired trophoblast invasion in early pregnancy is known to be closely associated with preeclampsia, the underlying mechanisms remain elusive. Here we revealed that lysyl oxidase (LOX) and LOX-like protein 2 (LOXL2) play a critical role in preeclampsia. Our results demonstrated that LOX and LOXL2 expression decreased in preeclamptic placentas. Moreover, knockdown of LOX or LOXL2 suppressed trophoblast cell migration and invasion. Mechanistically, collagen production was induced in LOX- or LOXL2-downregulated trophoblast cells through activation of the TGF-β1/Smad3 pathway. Notably, inhibition of the TGF-β1/Smad3 pathway could rescue the defects caused by LOX or LOXL2 knockdown, thereby underlining the significance of the TGF-β1/Smad3 pathway downstream of LOX and LOXL2 in trophoblast cells. Additionally, induced collagen production and activated TGF-β1/Smad3 were observed in clinical samples from preeclamptic placentas. Collectively, our study suggests that the downregulation of LOX and LOXL2 leading to reduced trophoblast cell migration and invasion through activa...Continue Reading

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Citations

Mar 19, 2020·Biomolecules·Susana M Chuva de Sousa LopesGudrun Valdimarsdottir
Jul 28, 2020·Biomolecules·Rozalia Laczko, Katalin Csiszar
Aug 23, 2020·International Journal of Molecular Sciences·Melisse ErasmusRabia Johnson
Feb 16, 2021·American Journal of Physiology. Renal Physiology·Catalina Sierra-RamosDiego Alvarez de la Rosa
Aug 25, 2021·Scientific Reports·Caixia ZhangHuang Li

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Methods Mentioned

BETA
deamination
cesarean section
urine collection
confocal microscopy
transfection
reverse-transcription PCR
enzyme-linked immunosorbent assay
electrophoresis
ELISA
enyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism
ImageJ
GraphPad

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