Significance of fibronectin 1 expression in gestational hypertension and
its effect on human umbilical vein endothelial cells
Abstract
Abstract Objective To explore the role of fibronectin 1(FN1) in
hypertensive disorder complicating pregnancy(HDCP) and human umbilical
vein endothelial cells(HUVECs). Methods Plasma FN1 of 80 HDCP women and
40 healthy pregnancy were detected by ELISA and its correlation with the
clinical data of HDCP were analyzed. Lentivirus vectors was transfected
into HUVECs to induce the overexpression of FN1. The levels of
proinflammatory cytokines TNF-ɑ, IL-6 were determined by ELISA and the
activity of MMP9 and MMP2 were detected by Gelatin zymography assay.
Apoptosis rate was analyzed by TUNEL, and Ad-mCherry-GFP-LC3 was
transfected to observe the autophagy. The expression of IKK-α, p-P65,
nuclear P65, EMT marker proteins: α-SMA, E-Cadeherin, Bcl2, Bax,
caspase-9, autophagy marker proteins:LC3Ⅱ, ATG5 and BENC1were detected
by western blot. Results Plasma FN1 in HDCP patients was high expressed
and it was increased with the development of HDCP. Overexpression of FN1
increased the expression of TNF-α, IL-6, IKK-α, p-P65, nuclear P65,
α-SMA and E-Cadeherin and the activity of MMP9 and MMP2. Overexpression
of FN1 induced apoptosis, upregulated the expression of caspase-9, Bax,
and downregulated Bcl-2. Overexpression of FN1 upregulated the
expression of LC3Ⅱ, ATG5 and BENC1, induced autophagosome formation and
inhibited autophagic degradation. MHY1485 could activate mTOR, to
reverse the induction of autophagy caused by overexpression of FN1.
Conclusion Plasma FN1 was related to the pathogenesis and progress of
HDCP. Overexpression of FN1 in HUVECs increased the inflammation,
induced the degradation of ECM, EMT and apoptosis, induced autophagosome
formation and inhibited autophagic degradation by inhibiting activation
of mTOR.