Tools
ToolsChen, Xuyang, Tao, Xinyi, Wang, Min, Cannon, Richard D., Chen, Bingnan, Yu, Xinyang, Qi, Hongbo, Saffery, Richard, Baker, Philip N., Zhou, Xiaobo, Han, Ting-Li and Zhang, Hua (2024) Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus. Journal of Nanobiotechnology, 22. ISSN 1477-3155
Preview |
PDF (s12951-024-02766-0)
- Published Version
Available under License Creative Commons Attribution. Download (7MB) | Preview |
Abstract
Background: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. Results: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3′-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain‐of‐function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. Conclusions: These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Funding information: This work was supported by the National Natural Science Foundation of China (No. 81971406, 81871185), The 111 Project (Yuwaizhuan (2016)32), Chongqing Science & Technology Commission (cstc2021jcyj-msxmX0213), Chongqing Municipal Education Commission (KJZD-K202100407), Chongqing Health Commission and Chongqing Science & Technology Commission (2021MSXM121, 2020MSXM101). |
| Uncontrolled Keywords: | extracellular vesicles,gestational diabetes mellitus,insulin resistance,fam3a,bioengineering,medicine (miscellaneous),molecular medicine,biomedical engineering,applied microbiology and biotechnology,pharmaceutical science ,/dk/atira/pure/subjectarea/asjc/1500/1502 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 08 May 2025 15:30 |
| Last Modified: | 09 May 2025 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99231 |
| DOI: | 10.1186/s12951-024-02766-0 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |