Association of β‐arrestin1 and p53‐Mdm2 signaling in the development of missed abortion

Abstract

Background Missed abortion is a nonviable pregnancy before the 20th week of gestation with retained products of conception. The de nite etiology and pathogenesis are not fully understood. β-arrestin1, the important dynamic multitask scaffold protein, it play an important regulatory role in interacting with G proteincoupled receptor (GPCR) to mediate its homologous desensitization and internalization. Recent studies have demonstrated that p53/Mdm2-mediated ubiquitination of the IGF-1R maybe closely related to G protein-coupled receptor kinases (GRK)/β-arrestin1 system. Our previous studies have con rmed 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 31 missed abortion patients and 31 healthy controls were determined by real-time quantitative PCR. Immunohistochemistry was used to explore the expression and location of β-arrestin1, p53, Mdm2, VEGF, HIF-lα in trophoblasts. We up-regulated and silenced the expression of β-arrestin1 by lentiviral transfection, transwell assays were performed to examine the in uences of β-arrestin1 expression on cell invasion. Furthermore, we explored the expression of several important proteins which may be related to β-arrestin1. Results β-arrestin1 mRNA levels in the villous samples from women with missed abortion were found to be dramatically lower than in women who had normal pregnancies. The immunohistochemistry results showed that β-arrestin1 positive staining was signi cantly lower in missed abortion group than that in normal pregnancies group. Furthermore, the patients with missed abortion showed signi cantly higher levels of p53, Mdm2 and HIF-lα, lower level of VEGF than healthy controls by immunohistochemistry. The protein expressions of pERK p-AKT p-p53 in HRT-8 cells were signi cantly downregulated by reducing β-arrestin1 expression, while the expression of p-NF-ΚB p-Mdm2 were enhanced. Overexpression of β-arrestin1 exhibited the adverse effect. The loss expression of β-arrestin1 expression was signi cantly related with decreased cell invasion ability. Conclusion Our data indicated that β-arrestin1 could play an important role in maintaining the maternal-fetal tolerance, the decreased β-arrestin1 expression in the villous samples may be related to the development of missed abortion.

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

“…Another study found that, β-arrestin2 deficiency in dendritic cells promotes migration and cytokine production which contributes to autoimmune encephalomyelitis ( Cai et al, 2019 ). The dysregulated expression of β-arrestin1 was found to be important in context of maternal-fetal tolerance in human pregnancies ( Liu et al, 2021 ) where a strongly reduced mRNA expression of β-arrestin1 was found in villous samples of missed abortion.…”

Research progress of E3 ubiquitin ligase regulating biological behavior of human placental trophoblast cells

“…MDM2 is an important gene that regulates p53 pathway, has the function of p53 degradation and ubiquitination, participates in the occurrence and development of tumors, and is related to embryonic development and tissue differentiation ( 29 ). Recent research shows that p53/Mdm2 system can mediate β-arrestin1 expression, which plays an important role in maintaining maternal-fetal tolerance, the decreased expression of β-arrestin1 in the villous samples may be related with the development of missed abortion ( 30 ).…”