# TRIM28-mediated p53 ubiquitination inhibits trophoblast apoptosis to support normal placental development

## TL;DR

TRIM28 helps prevent trophoblast cell death in the placenta, which could protect against early-onset preeclampsia.

## Contribution

TRIM28 inhibits p53 activity to reduce trophoblast apoptosis during oxidative stress in placental development.

## Key findings

- TRIM28 expression is reduced in placentas of early-onset preeclampsia mouse models.
- TRIM28 suppresses p53 to downregulate pro-apoptotic proteins and upregulate anti-apoptotic Bcl-2.
- TRIM28 reduces hydrogen peroxide-induced apoptosis in trophoblast cells by promoting p53 ubiquitination.

## Abstract

Tripartite motif-containing 28 (TRIM28), a transcriptional regulatory factor, is involved in various biological processes. However, its role in early-onset preeclampsia (EOPE) remains unclear. An EOPE mouse model was established using Nω-Nitro-L-arginine methyl ester (L-NAME), while TRIM28 or tumor protein p53 (p53) expression was modulated through lentiviral infections. Maternal blood pressure and urinary protein levels were measured. Placental tissues were collected at embryonic day 17.5 for hematoxylin-eosin staining, immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction. In vitro, HTR-8/SVneo trophoblast cells were exposed to hydrogen peroxide (H2O2) to simulate oxidative stress. TRIM28 and p53 were overexpressed via lentiviral vectors, and cell apoptosis and molecular changes were assessed. TRIM28 expression was significantly downregulated in placentas from EOPE mice. Mechanistically, TRIM28 suppressed p53 level, downregulating pro-apoptotic proteins Bcl-2-associated X protein (Bax) and cleaved caspase-3, while upregulating the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). In trophoblast cells, TRIM28 alleviated H2O2-induced apoptosis by promoting p53 ubiquitination and thereby reducing its pro-apoptotic activity. TRIM28 attenuates oxidative stress-induced trophoblast apoptosis and may help protect against the development of EOPE.