Identifying and validating the key regulatory transcription factor YY1 in the aging process of pancreatic beta cells based on bioinformatics
The aging of pancreatic beta cells is closely associated with various diseases, such as impaired glucose tolerance, yet the underlying regulatory mechanisms remain unclear. In this study, we screened young and aged mouse pancreatic beta cells' high-throughput sequencing data from the GEO public database. Utilizing bioinformatics techniques, we identified the key regulatory factor YY1 in the aging process of pancreatic islets. We observed a significant decrease in the expression of YY1 in a D-gal-induced mouse model of pancreatic aging and an H<sub>2</sub>O<sub>2</sub>-induced MIN6 cell model of aging. Moreover, both vivo and vitro models, we found that the YY1 agonist eudesmin (EDN) improved glucose intolerance in mice, alleviated aging of pancreatic beta cells, and downregulated the expression of cell cycle protein P21. Mechanistically, we discovered that EDN inhibited the P38/JNK MAPK pathway in aging cells. In summary, our study confirms the regulatory role of the transcription factor YY1 in the aging process of pancreatic beta cells. This finding may provide a new approach for the clinical treatment of pancreatic aging-related diseases such as impaired glucose tolerance or diabetes.
Authors
- Weijuan Gong (ORCID: https://orcid.org/0000-0002-8543-1314)
- Guotao Lu (ORCID: https://orcid.org/0000-0002-8325-0405)
- Jun‐Qi Yang (ORCID: https://orcid.org/0000-0002-4510-8117)
- Shan Qing (ORCID: https://orcid.org/0000-0002-7700-0143)
- Weiming Xiao (ORCID: https://orcid.org/0000-0002-8893-9076)
- Yanbing Ding (ORCID: https://orcid.org/0000-0002-0689-2199)
- Chenchen Yuan (ORCID: https://orcid.org/0000-0002-0551-0718)
- Qingtian Zhu (ORCID: https://orcid.org/0000-0002-1302-8489)
- Hongwei Xu (ORCID: https://orcid.org/0000-0002-0470-705X)
- Rui Zhou (ORCID: https://orcid.org/0000-0002-4333-4137)
- Yumin Ma
- Jiang Liu (ORCID: https://orcid.org/0000-0001-8873-2553)
Institutions
- Shanghai University of Traditional Chinese Medicine (CN)
- Traditional Chinese Medicine Hospital of Kunshan (CN)
- Northern Jiangsu People's Hospital (CN)
- Yangzhou University (CN)
Publication Details
- Journal
- Experimental Gerontology
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1016/j.exger.2024.112633
- Citations
- 1
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.57
Funders
- National Natural Science Foundation of China