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Updated: Aug 14, 2025
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Transient receptor potential melastatin 7 aggravates necrotizing enterocolitis by promoting an inflammatory response
Qingxiang Li1,2, Xianming Lei1,2, Hong Liu1,2
1Department of Neonatology, Guizhou Children's Hospital, Zunyi, China.
Insights
Necrotizing enterocolitis (NEC) in children involves increased Transient Receptor Potential Melastatin 7 (TRPM7) and NLRP3 inflammasome activation. A TRPM7 inhibitor, NS8593, demonstrated therapeutic potential by reducing inflammation and protecting against NEC.
Area of Science:
- Pediatric Gastroenterology
- Molecular Biology
- Inflammation Research
Background:
- Necrotizing enterocolitis (NEC) is a severe condition in infants with high mortality.
- The exact pathophysiology of NEC remains largely unknown.
- Transient Receptor Potential Melastatin 7 (TRPM7) is implicated in inflammatory processes.
Purpose of the Study:
- To investigate the role of TRPM7 in pediatric NEC.
- To explore the therapeutic efficacy of the TRPM7 inhibitor NS8593 in NEC.
Main Methods:
- Assessed TRPM7 and NLRP3 expression and inflammation markers in NEC patients via RT-PCR, Western blot, and ELISA.
- Induced NEC in human intestinal cell lines and a rat model using lipopolysaccharides (LPS).
- Evaluated the effects of TRPM7 inhibition on cytokine production, reactive oxygen species (ROS), and inflammasome activation.
Main Results:
- Elevated TRPM7 and NLRP3 expression and increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were observed in children with NEC.
- TRPM7 inhibition by NS8593 reduced LPS-induced cytokine release and NLRP3 inflammasome activation in cell lines.
- In vivo studies showed TRPM7 involvement in NEC pathogenesis and a therapeutic effect of NS8593 in a rat model.
Conclusions:
- TRPM7 plays a promoting role in NEC development, potentially through NLRP3 inflammasome activation.
- TRPM7 inhibitors like NS8593 can attenuate LPS-induced inflammation, reduce ROS, and offer protective effects in NEC models.
Background:
As a rare disease in children, necrotizing enterocolitis (NEC) leads to high morbidity and mortality. However, its pathophysiology is largely unclear. Transient receptor potential melastatin 7 (TRPM7) is a membrane protein, which plays key roles in the inflammatory response. This study sought to examine the promoting effect of TRPM7 on NEC in children and explore the therapeutic effect of a TRPM7 inhibitor NS8593.
Methods:
First, we detected TRPM7 and NLR family pyrin domain containing 3 (NLRP3) expression and the state of inflammation in children with NEC through quantitative real-time polymerase chain reaction (RT-PCR), Western blot, and enzyme-linked immunosorbent assays. Next, Human intestinal epithelial cell lines were induced to NEC by lipopolysaccharides (LPSs). The level of cytokines and reactive oxygen species (ROS) were tested by RT-PCR and flow cytometry. The TRPM7 mediated calcium flux were determined by fluorescence. In addition, we used the TRPM7 inhibitor NS8593 to treat the in vivo rat model. The mRNA and protein expression were determined by real-time PCR and Elisa analysis, respectively.
Results:
TRPM7 and NLRP3 expression was more increased in the samples from children with NEC compared to the control samples. Additionally, the elevated secretion of interleukin-1β, interleukin-6, and tumor necrosis factor alpha was also detected in the serum of children with NEC. These results showed that TRPM7 had a promoting effect on NEC development, possibly via the activation of NLRP3. To test our hypothesis, the TRPM7 inhibitor NS8593 was used to treat the LPS-stimulated IEC-6 cells. We found that the TRPM7 inhibitor NS8593 inhibited LPS-induced cytokine production and exhibited an anti-inflammatory effect by alleviating TRPM7-mediated NLRP3 inflammasome activation. Through in-vivo experiments, we found that TRPM7 was involved in the occurrence of NEC, and its inhibitor NS8593 played a certain therapeutic role in the rat model.
Conclusions:
Our study revealed TRPM7 inhibitors attenuated LPS-induced ROS and reduced the release of pro-inflammatory cytokines. It also exhibited protective effects on the NEC model.
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