FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis.
- Author:
Ping-Ping WU
1
;
Wen-Long HU
2
,
3
;
Chang-Chang YIN
4
;
Jiu-Wang FEI
4
Author Information
1. Department of Orthopaedics, Jiujiang University Affiliated Hospital, Jiujiang 332000, China.
2. Department of Orthopaedics, Jiujiang University Affiliated Hospital, Jiujiang 332000, China. huwenlong1988@
3. com.
4. Department of Biochemistry, College of Basic Medicine, Jiujiang University, Jiujiang 332000, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Cell Cycle Proteins;
Cell Survival;
Cellular Senescence;
Forkhead Transcription Factors;
Humans;
Mesenchymal Stem Cell Transplantation;
Mesenchymal Stem Cells;
Transcription Factors;
Umbilical Cord
- From:
Acta Physiologica Sinica
2020;72(4):426-432
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by β-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.
