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

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...

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Autores principales: MA, YUHANG, WANG, XUEJIAO, PENG, YONGDE, DING, XIAOYING
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805100/
https://www.ncbi.nlm.nih.gov/pubmed/26935354
http://dx.doi.org/10.3892/mmr.2016.4896
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author MA, YUHANG
WANG, XUEJIAO
PENG, YONGDE
DING, XIAOYING
author_facet MA, YUHANG
WANG, XUEJIAO
PENG, YONGDE
DING, XIAOYING
author_sort MA, YUHANG
collection PubMed
description 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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spelling pubmed-48051002016-04-04 Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24 MA, YUHANG WANG, XUEJIAO PENG, YONGDE DING, XIAOYING Mol Med Rep Articles 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. D.A. Spandidos 2016-04 2016-02-16 /pmc/articles/PMC4805100/ /pubmed/26935354 http://dx.doi.org/10.3892/mmr.2016.4896 Text en Copyright: © Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
MA, YUHANG
WANG, XUEJIAO
PENG, YONGDE
DING, XIAOYING
Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title_full Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title_fullStr Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title_full_unstemmed Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title_short Forkhead box O1 promotes INS-1 cell apoptosis by reducing the expression of CD24
title_sort forkhead box o1 promotes ins-1 cell apoptosis by reducing the expression of cd24
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805100/
https://www.ncbi.nlm.nih.gov/pubmed/26935354
http://dx.doi.org/10.3892/mmr.2016.4896
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AT pengyongde forkheadboxo1promotesins1cellapoptosisbyreducingtheexpressionofcd24
AT dingxiaoying forkheadboxo1promotesins1cellapoptosisbyreducingtheexpressionofcd24