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FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis

WU Ping-Ping¹, HU Wen-Long^1,*, YIN Chang-Chang², FEI Jiu-Wang²

¹Department of Orthopaedics, Jiujiang University Affiliated Hospital, Jiujiang 332000, China；²Department of Biochemistry, College of Basic Medicine, Jiujiang University, Jiujiang 332000, China

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.

Key words: human umbilical cord-derived mesenchymal stem cells; forkhead box O4; cellular senescence; apoptosis

Received: 2019-08-25　　Accepted: 2019-12-25

Corresponding author: 胡文龙　　E-mail: huwenlong1988@126.com

DOI: 10.13294/j.aps.2020.0045

Citing This Article：

WU Ping-Ping, HU Wen-Long, YIN Chang-Chang, FEI Jiu-Wang. FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis. Acta Physiol Sin 2020; 72 (4): 426-432 (in Chinese with English abstract).