Upregulated ARRDC3 limits trophoblast cell invasion and tube formation and is associated with preeclampsia.

Abstract:

OBJECTIVE:Bioinformatics analysis indicated that the arrestin ARRDC3 was upregulated in placental tissue from patients with preeclampsia (PE). The study aimed to confirm the finding by examining placenta samples from women with and without early-onset PE and to investigate ARRDC3 roles in trophoblast function. METHODS:ARRDC3 expression level and localization in placental tissue were determined by Western blot, real-time quantitative PCR and immunohistochemistry. An in vitro hypoxia and an in vitro ischemia (hypoxia/reoxygenation) cell models were used to determine the hypoxic and ischemic effects on ARRDC3 expression in extravillous trophoblast-derived HTR/8SVneo cells and trophoblast cell activity. The role of ARRDC3 in HTR8/SVneo cell proliferation, invasion and tube formation in vitro was investigated by testing the effects of ARRDC3 gene overexpression or siRNA-based gene silencing. RESULTS:ARRDC3 expression was significantly elevated in placental tissue from women with early-onset PE compared to preterm birth pregnancies. ARRDC3 protein was localized in human placental trophoblasts. Hypoxia and ischemia both enhanced ARRDC3 protein expression in HTR8/SVneo cells. Hypoxia altered trophoblast cell activities. Overexpression of ARRDC3 in HTR8/SVneo cells suppressed cell invasion and tube formation. ARRDC3 gene silencing, by contrast, promoted invasion and tube formation under hypoxic conditions. CONCLUSION:ARRDC3 was highly expressed in placental tissues of PE patients and directly affected biological activities of trophoblasts under hypoxic conditions. In regulation of ARRDC3- protein expression, ischemia (hypoxia/reoxygenation) are also important. These findings suggest that ARRDC3 may play a clinically significant role in the pathogenesis of PE.

journal_name

Placenta

journal_title

Placenta

authors

Lei D,Deng N,Wang S,Huang J,Fan C

doi

10.1016/j.placenta.2019.10.009

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

10-19

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(19)30681-2

journal_volume

89

pub_type

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