The Pathophysiology of Antiphospholipid Syndrome

Sada, Pablo Ruiz; Cohen, Hannah; Isenberg, David

doi:10.2174/1874303x01508010002

Cited by 2 publications

(1 citation statement)

References 92 publications

(103 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This closed structure is altered to form an open structure when domain V of β2-GP binds to a lipid layer and domains I–IV expose the potential binding site for aβ2-GP I ( 21 ). Fetal loss may occur when β2-GP I binds to its antibody aβ2-GP I, which results in thrombogenesis, hypercoagulability and inhibition of growth, differentiation, invasion and migration of trophoblast cells ( 22 – 24 ). However, the mechanism underlying these reactions remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Effect and mechanism of the aβ2‑GP I/rhβ2‑GP I complex on JEG‑3 cell proliferation, migration and invasion

Ren

Zhang

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Antiphospholipid antibody (aPL)-mediated antiphospholipid syndrome (APS) is an autoimmune disease. Upon binding to aPL, the primary antigen of aPL, β2-glycoprotein I (β2-GP I), induces abnormal immune function, which further activates downstream signaling pathways in the cell and eventually leads to APS. The present study aimed to determine whether β2-GP I antigen and anti-β2-glycoprotein I antibody (aβ2-GP I), which belong to the aPL class of antibodies, may affect human chorionic epithelium cell (JEG-3) proliferation, migration and invasion. Recombinant human (rh)β2-GP I protein was expressed using a prokaryotic expression system and aβ2-GP I antibody was purified from the blood serum of 10 patients with recurrent pregnancy loss. JEG-3 cells were stimulated with rhβ2-GP I and aβ2-GP I separately or simultaneously, and serum immunoglobulin G of normal pregnant women was used as negative control. Using cell counting kit-8, cell cycle and transwell assays in addition to EdU staining, it was determined that aβ2-GP I/rhβ2-GP I complex markedly increased JEG-3 cell proliferation, migration and invasion. The results revealed that mRNA levels of inhibitor of nuclear factor (NF)-κB kinase subunit (IKKβ), myeloid differentiation primary response protein MyD88 (MyD88), NF-κB and NF-κB inhibitor α (IκBα), as well as the protein levels of MyD88, IκBα and phospho(p)-IκBα in JEG-3 cells increased following incubation with the aβ2-GP I/rhβ2-GP I complex. The observed upregulation of p-IκBα protein suggested that IκBα-mediated inhibition of NF-κB was weakened. Furthermore, JEG-3 cells were transfected with PGMLV-NF-κB-Lu vector. Luciferase activity in JEG-3-NFκB-Luc1 and JEG-3-NFκB-Luc2 cells was enhanced following treatment with aβ2-GP I/rhβ2-GP I complex. The present study demonstrated that aβ2-GP I/rhβ2-GP I complex activates NF-κB through MyD88 signal transduction pathway, which further enhances JEG-3 cell proliferation, migration and invasion.

show abstract

Section: Discussionmentioning

confidence: 99%