Chorionic villus-derived mesenchymal stem cells induce E3 ligase TRIM72 expression and regulate cell behaviors through ubiquitination of p53 in trophoblasts.

Abstract

Preeclampsia is a significant contributor for maternal or fetal morbidity and mortality, which is characterized by reduced invasion capacity of trophoblasts and is regulated by extracellular matrix (ECM). It is still under investigation whether chorionic villus-derived mesenchymal stem cells (CVMSC) could affect the functionality of trophoblasts. In this study, CVMSC-derived exosomes were isolated; their effect on trophoblasts was investigated based on the CCK8 assay, migration assay, and apoptosis detection. And the underlying mechanism of this effect was investigated using mRNA sequencing, western blot, co-immunoprecipitation, luciferase report assay, and ubiquitination assay. The results show that CVMSC-derived exosomes promote migration and proliferation of trophoblasts, and also reduce cell apoptosis. mRNA sequencing confirmed that after treatment of CVMSC-derived exosomes, Tripartite Motif Containing 72 (TRIM72) expression was upregulated and Tumor Protein P53 (P53) expression was downregulated, both significantly in trophoblasts. Subsequent study confirms that TRM72 can directly interact with P53 and promote P53 ubiquitination and proteasomal degradation, reducing apoptosis rate and elevating proliferation and migration in trophoblasts. Our study confirms that CVMSC-derived exosomes promote trophoblast migration and proliferation by upregulating TRIM72 expression, and subsequently advance P53 ubiquitination and proteasomal degradation.

• Authors: Yan Li, Chen Wang, Hong-Min Xi, Wen-Ting Li, Ya-Jun Liu, Shan Feng, Yi-Jing Chu, Yi-Hao Wang
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 35 Issue 12 Pg. e22005 (12 2021) ISSN: 1530-6860 [Electronic] United States
• PMID: 34788479 (Publication Type: Journal Article)
• Copyright: © 2021 Federation of American Societies for Experimental Biology.

Chemical References

• TP53 protein, human
• TRIM72 protein, human
• Tripartite Motif Proteins
• Tumor Suppressor Protein p53

Topics

• Apoptosis
• Cell Movement
• Cell Proliferation
• Chorionic Villi (growth & development, metabolism)
• Exosomes (metabolism)
• Female
• Humans
• Mesenchymal Stem Cells (cytology, metabolism)
• Pregnancy
• Tripartite Motif Proteins (genetics, metabolism)
• Trophoblasts (cytology, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Ubiquitination