Association of β-arrestin1 and p53-Mdm2 signaling in the development of missed abortion
| Autor: | Qihui Yin, Yan Fang, Ting Liu, Yuyan Ma, Huanyu Zhou |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
MAPK/ERK pathway
Apoptosis Abortion Pathogenesis Andrology 03 medical and health sciences 0302 clinical medicine Pregnancy Medicine Humans Receptor Protein kinase B 030219 obstetrics & reproductive medicine business.industry Kinase NF-kappa B Obstetrics and Gynecology Proto-Oncogene Proteins c-mdm2 Real-time polymerase chain reaction beta-Arrestin 1 030220 oncology & carcinogenesis Immunohistochemistry Female Abortion Missed Tumor Suppressor Protein p53 business Signal Transduction |
| Zdroj: | The journal of obstetrics and gynaecology researchReferences. 47(5) |
| ISSN: | 1447-0756 |
| Popis: | BackgroundMissed abortion is a nonviable pregnancy before the 20th week of gestation with retained products of conception. The definite 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 protein-coupled 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 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.MethodsThe 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 influences of β-arrestin1 expression on cell invasion. Furthermore, we explored the expression of several important proteins which may be related to β-arrestin1.Resultsβ-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 significantly lower in missed abortion group than that in normal pregnancies group. Furthermore, the patients with missed abortion showed significantly higher levels of p53, Mdm2 and HIF-lα, lower level of VEGF than healthy controls by immunohistochemistry. The protein expressions of p-ERK、p-AKT、p-p53 in HRT-8 cells were significantly 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 significantly related with decreased cell invasion ability.ConclusionOur 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text