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Chorionic villus-derived mesenchymal stem cells induce E3 ligase TRIM72 expression and regulate cell behaviors through ubiquitination of p53 in trophoblasts.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Dec; Vol. 35 (12), pp. e22005. - Publication Year :
- 2021
-
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.<br /> (© 2021 Federation of American Societies for Experimental Biology.)
- Subjects :
- Apoptosis
Cell Movement
Cell Proliferation
Chorionic Villi growth & development
Female
Humans
Mesenchymal Stem Cells cytology
Pregnancy
Tripartite Motif Proteins genetics
Trophoblasts cytology
Tumor Suppressor Protein p53 genetics
Chorionic Villi metabolism
Exosomes metabolism
Mesenchymal Stem Cells metabolism
Tripartite Motif Proteins metabolism
Trophoblasts metabolism
Tumor Suppressor Protein p53 metabolism
Ubiquitination
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 35
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 34788479
- Full Text :
- https://doi.org/10.1096/fj.202100801R