Related Experiment Video
Updated: May 31, 2025
Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Tetrahedral Framework Nucleic Acid Relieves Sepsis-Induced Intestinal Injury by Regulating M2 Macrophages
Tingting Tan1,2,3, Jiajie Li4, Wensi Fan1
1Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Abstract:
This study aimed to clarify the role and mechanism of tetrahedral framework nucleic acids (tFNAs) in regulating M2 macrophages to reduce intestinal injury. An intestinal injury model was established by intraperitoneal injection of lipopolysaccharides (LPS) in mice to explore the alleviating effects of tFNAs on intestinal injury. Inflammatory factors were detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The intestinal barrier and permeability were assessed using western blotting and immunohistochemistry. Macrophages in the gut were localised and quantified using immunofluorescence. Western blotting was used to investigate the role and mechanism of tFNAs in regulating macrophages and alleviating inflammation in the injured intestines. These results show that tFNAs attenuated sepsis-induced intestinal injury. tFNAs can also promote the intestinal barrier reconstruction and reduce intestinal permeability. In vivo, tFNAs accelerated the aggregation of M2 macrophages at an early stage of injury and reduced the number of M1 macrophages in the intestine. In addition, tFNAs enhanced the clearance ability of intestinal macrophages. They activated the signalling and transcription activating factor 1(STAT1) and cytokine signalling inhibitory factor 1/3 (SOCS1/3) pathways by increasing the expression of the phagocytic receptor Mertk. These findings indicated that tFNAs can alleviate sepsis-induced intestinal injury by regulating M2 macrophages, providing a new option for treating intestinal injury.
Insights
Tetrahedral framework nucleic acids (tFNAs) reduce intestinal injury by promoting M2 macrophage aggregation and enhancing gut barrier function. These findings offer a novel therapeutic strategy for treating sepsis-induced intestinal damage.
Area of Science:
- Biomedical Engineering
- Immunology
- Gastroenterology
Background:
- Sepsis-induced intestinal injury is a critical complication with significant mortality.
- Modulating macrophage polarization, particularly towards the M2 phenotype, is a promising therapeutic avenue for tissue repair.
Purpose of the Study:
- To elucidate the mechanism by which tetrahedral framework nucleic acids (tFNAs) regulate M2 macrophages to mitigate intestinal injury.
- To evaluate the therapeutic potential of tFNAs in a mouse model of sepsis-induced intestinal injury.
Main Methods:
- Establishment of a lipopolysaccharide (LPS)-induced mouse model of intestinal injury.
- Assessment of inflammatory factors using qPCR and ELISA.
- Evaluation of intestinal barrier integrity and permeability via Western blotting and immunohistochemistry.
- Quantification and localization of macrophages using immunofluorescence.
- Investigation of tFNAs' regulatory mechanisms on macrophages and inflammation through Western blotting.
Main Results:
- tFNAs significantly attenuated sepsis-induced intestinal injury and promoted intestinal barrier reconstruction.
- tFNAs enhanced M2 macrophage aggregation and M1 macrophage reduction in injured intestines.
- tFNAs improved the clearance capacity of intestinal macrophages by activating STAT1 and SOCS1/3 pathways via Mertk receptor upregulation.
Conclusions:
- tFNAs demonstrate a therapeutic effect on sepsis-induced intestinal injury by reprogramming macrophages towards an M2 phenotype.
- tFNAs enhance intestinal barrier function and macrophage-mediated clearance, presenting a novel therapeutic strategy for intestinal injury.
