PMID- 32820304 OWN - NLM STAT- MEDLINE DCOM- 20200924 LR - 20220531 IS - 0371-0874 (Print) IS - 0371-0874 (Linking) VI - 72 IP - 4 DP - 2020 Aug 25 TI - [FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis]. PG - 426-432 AB - 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 beta-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. FAU - Wu, Ping-Ping AU - Wu PP AD - Department of Orthopaedics, Jiujiang University Affiliated Hospital, Jiujiang 332000, China. FAU - Hu, Wen-Long AU - Hu WL AD - Department of Orthopaedics, Jiujiang University Affiliated Hospital, Jiujiang 332000, China. huwenlong1988@126.com. FAU - Yin, Chang-Chang AU - Yin CC AD - Department of Biochemistry, College of Basic Medicine, Jiujiang University, Jiujiang 332000, China. FAU - Fei, Jiu-Wang AU - Fei JW AD - Department of Biochemistry, College of Basic Medicine, Jiujiang University, Jiujiang 332000, China. LA - chi PT - Journal Article PL - China TA - Sheng Li Xue Bao JT - Sheng li xue bao : [Acta physiologica Sinica] JID - 20730130R RN - 0 (Cell Cycle Proteins) RN - 0 (FOXO4 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Transcription Factors) SB - IM MH - *Apoptosis MH - Cell Cycle Proteins MH - Cell Survival MH - Cellular Senescence MH - Forkhead Transcription Factors MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Transcription Factors MH - Umbilical Cord EDAT- 2020/08/21 06:00 MHDA- 2020/09/25 06:00 CRDT- 2020/08/22 06:00 PHST- 2020/08/22 06:00 [entrez] PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/09/25 06:00 [medline] PST - ppublish SO - Sheng Li Xue Bao. 2020 Aug 25;72(4):426-432.