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Association of β‐arrestin1 and p53‐Mdm2 signaling in the development of missed abortion
Author(s) -
Liu Ting,
Ma Yuyan,
Yin Qihui,
Zhou Huanyu,
Fang Yan
Publication year - 2021
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.14643
Subject(s) - immunohistochemistry , medicine , abortion , mdm2 , mapk/erk pathway , protein kinase b , real time polymerase chain reaction , pathogenesis , apoptosis , andrology , kinase , cancer research , pathology , biology , pregnancy , microbiology and biotechnology , gene , genetics
Background Missed abortion is a peculiar form of spontaneous abortion before 20 weeks' gestation. The definite etiology and pathogenesis are not fully understood. Recent studies have demonstrated that p53/Mdm2‐mediated ubiquitination of the IGF‐1R may be closely related to G‐protein‐coupled receptor kinases (GRK)/β‐arrestin1 system. Our previous studies have confirmed that the elevated expression of p53 and Mdm2 may be responsible for apoptosis during missed abortion. However, there was no information surrounding β‐arrestin1 in missed abortion. Methods The mRNA levels of β‐arrestin1 in villous samples of 30 missed abortion patients and 31 healthy controls were determined by real‐time quantitative polymerase chain reaction (PCR). Immunohistochemistry was used to explore the expression and location of β‐arrestin1, p53, Mdm2, VEGF and HIF‐lα in trophoblasts. Transwell assays were performed to examine the influences of β‐arrestin1 expression on cell invasion. Furthermore, we tested the effect of β‐arrestin1 on the expression of p53, Mdm2, ERK, AKT and NF‐κB. Results The expression of β‐arrestin1 in the villous samples of missed abortion group was dramatically lower than control group by quantitative real‐time‐PCR and immunohistochemistry. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2, HIF‐lα and lower level of VEGF than healthy controls by immunohistochemistry. Functional studies showed that suppression of β‐arrestin1 in HTR‐8 cells inhibited cell invasion. The protein expressions of ERK and AKT in HTR‐8 cells were significantly downregulated by reducing the expression of β‐arrestin1, while the expressions of p53, Mdm2, NF‐κB were enhanced. Overexpression of β‐arrestin1 exhibited the adverse effect. Conclusion Our data indicated that β‐arrestin1 play an important role in maintaining the maternal‐fetal tolerance, the decreased expression of β‐arrestin1 in the villous samples may be related with the development of missed abortion.