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Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier
Zhihua Liu1,2,3, Yinghai Tian4, Yanqiong Jiang5
1Department of AnoRectal Surgery, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Background/Aims:
Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction.
Methods:
A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot.
Results:
Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function.
Conclusion:
Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.
Insights
Let-7b, a microRNA, plays a crucial role in maintaining intestinal barrier function by targeting p38 MAPK. Restoring let-7b levels may offer a therapeutic strategy for intestinal barrier dysfunction.
Area of Science:
- Gastroenterology
- Molecular Biology
- Microbiology
Background:
- Intestinal barrier dysfunction is a critical issue in various gastrointestinal diseases.
- Let-7b microRNA levels are significantly reduced in conditions of intestinal injury.
- The precise molecular mechanisms underlying let-7b's role in intestinal barrier integrity remain to be fully elucidated.
Purpose of the Study:
- To investigate the molecular mechanism by which let-7b influences intestinal barrier function.
- To determine if let-7b targets the p38 MAPK signaling pathway.
- To explore the therapeutic potential of let-7b in preventing intestinal barrier dysfunction.
Main Methods:
- Human subjects (n=186) and a mouse model (let-7b IKO mice) were utilized.
- Serum and tissue levels of let-7b, zonulin, IL-6, and TNF-α were quantified.
- Intestinal permeability, tight-junction protein expression, and apoptosis were assessed.
Main Results:
- Probiotics increased serum and tissue let-7b levels and reduced complications.
- Let-7b directly targets and negatively regulates p38 MAPK signaling.
- In let-7b IKO mice, p38 MAPK expression increased, while tight-junction proteins decreased.
Conclusions:
- Let-7b is a key regulator of intestinal barrier function through the p38 MAPK pathway.
- Let-7b serves as a potential diagnostic biomarker for intestinal barrier dysfunction.
- Modulating let-7b levels presents a promising therapeutic target for intestinal barrier repair.
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