| Title: | LncRNA Gm16023 ameliorates hyperglycemia-exacerbated septic intestinal injury by modulating macrophage polarization via miR-377-3p/Sirt1 axis |
| Journal: | Molecular Therapy |
| Published: | 27 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41764071/ |
| DOI: | https://doi.org/10.1016/j.ymthe.2026.02.042 |
Publication 17596
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Diabetes is closely associated with inflammation and sepsis, but its clinical significance and underlying mechanisms remain obscure. Leveraging epidemiological data from 404,184 individuals in the UK Biobank cohort, we found that hyperglycemia was significantly associated with increased sepsis risk. Phenotypically, hyperglycemia enhanced macrophage infiltration and exacerbated intestinal inflammation in both septic patients and murine models. Using both a genetic CD11b-DTR model and clodronate liposome-mediated chemical ablation, we demonstrated that macrophage depletion markedly attenuated hyperglycemia-driven septic intestinal injury, underscoring their essential pathogenic role. Mechanistically, RNA sequencing analysis identified that underexpressed lncRNA Gm16023 acted as a ceRNA, binding miR-377-3p to regulate Sirt1 expression and inhibit M1 macrophage polarization. To facilitate therapeutic delivery, we engineered a lipid nanoparticle-encapsulated Gm16023 plasmid system that efficiently delivered lncRNA in vivo and conferred protection against intestinal injury in both in vitro and in vivo models. Collectively, our findings indicate that hyperglycemia promotes macrophage-mediated septic intestinal injury via the lncRNA Gm16023/miR-377-3p/Sirt1 axis, highlighting a potential RNA-based therapeutic strategy for diabetic sepsis.</p>
11 Authors
- Fang Tan
- Lei Zheng
- Dongdong Yuan
- Shuang Wang
- Weifeng Yao
- Tao Wang
- Bin Xia
- Ningning Li
- Zhang Fu
- Tufeng Chen
- Xinjin Chi
1 Application
| Application ID | Title |
|---|---|
| 51671 | Metabolism syndrome and risk of cancer |
Enabling scientific discoveries that improve human health