Forkhead box O1 promotes INS‑1 cell apoptosis by reducing the expression of CD24

Ma,Yuhang; Wang,Xuejiao; Peng,Yongde; Ding,Xiaoying

doi:10.3892/mmr.2016.4896

Forkhead box O1 promotes INS‑1 cell apoptosis by reducing the expression of CD24

Authors:
- Yuhang Ma
- Xuejiao Wang
- Yongde Peng
- Xiaoying Ding
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Affiliations: Department of Endocrinology and Metabolism, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China
Published online on: February 16, 2016 https://doi.org/10.3892/mmr.2016.4896
Pages: 2991-2998
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Type 2 diabetes seriously affects human health and burdens public health systems. Pancreatic β‑cell apoptosis contributes to a reduction in β‑cell mass, which is responsible for the occurrence of type 2 diabetes. However, the mechanism that underlies this effect remains unclear. In the present study, the role of forkhead box O1 (Foxo1) was investigated (which is a key regulatory factor in β‑cell function) in the apoptotic behavior of β‑cells and a potential underlying mechanism was determined. It was demonstrated that Foxo1 overexpression significantly reduced the proliferation of INS‑1 cells and increased the apoptosis of INS‑1 cells, in contrast to foxm1, foxp, foxa1, foxc and foxb1 overexpression. The present study aimed to investigate potential underlying mechanisms using bioinformatics, including Gene Set Enrichment Analysis, and biological experiments, including flow cytometry, cell counting kit‑8, immunofluorescence, western blotting, reverse transcription‑quantitative polymerase chain reaction analysis and lentiviral transfection. Further experiments conclusively showed that cluster of differentiation (CD)24 expression was significantly decreased when INS‑1 cells were treated with Foxo1. Animal experiments showed high CD24 expression in the pancreatic islets of diabetic Goto‑Kakizaki rats. Moreover, Gene Set Enrichment Analysis showed that CD24 expression was associated with the adaptive immune response of β‑cells. Finally, no significant differences in the proliferation and apoptosis of CD24 overexpressing INS‑1 cells were observed after Foxo1 treatment. These results suggested that Foxo1 overexpression in β‑cells was able to increase apoptosis by inhibiting CD24 expression. This study may provide an approach for the treatment and prevention of type 2 diabetes.

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