2. Academic Validation
  3. Toll-Like Receptor 2 Deficiency Exacerbates Dextran Sodium Sulfate-Induced Intestinal Injury through Marinifilaceae- Dependent Attenuation of Cell Cycle Signaling

Toll-Like Receptor 2 Deficiency Exacerbates Dextran Sodium Sulfate-Induced Intestinal Injury through Marinifilaceae- Dependent Attenuation of Cell Cycle Signaling

  • Front Biosci (Landmark Ed). 2024 Sep 24;29(9):338. doi: 10.31083/j.fbl2909338.
Yun-Jie Shi 1,  Kai-Wen Sheng 1,  Hai-Nan Zhao 2,  Cong Liu 3,  Hao Wang 1
Affiliations

Affiliations

  • 1 Department of Colorectal Surgery, The First Affiliated Hospital (Changhai Hospital), Naval Medical University, 200433 Shanghai, China.
  • 2 Department of Radiology Intervention, The First Affiliated Hospital (Changhai Hospital), Naval Medical University, 200433 Shanghai, China.
  • 3 Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 200433 Shanghai, China.
PMID: 39344335 DOI: 10.31083/j.fbl2909338
Abstract

Background: Ulcerative colitis (UC) is an intestinal disorder marked by chronic, recurring inflammation, yet its underlying mechanisms have not been fully elucidated.

Methods: The current research dealt with examining the biological impacts of Toll-like Receptor 2 (TLR2) on dextran sulfate sodium (DSS)-triggered inflammation in the intestines of wild-type (WT) and TLR2-knockout (TLR2-KO) colitis mouse models. To elucidate the protective function of TLR2 in DSS-triggered colitis, RNA-sequencing (RNA-Seq) was carried out to compare the global gene expression data in the gut of WT and TLR2-KO mice. Further, 16S rRNA gene Sequencing revealed notable variations in gut microbiota composition between WT and TLR2-KO colitis mice.

Results: It was revealed that TLR2-KO mice exhibited increased susceptibility to DSS-triggered colitis. RNA-Seq results demonstrated that cell cycle pathway-related genes were notably downregulated in TLR2-KO colitis mice (enrichment score = 30, p < 0.001). 16S rRNA gene Sequencing revealed that in comparison to the WT colitis mice, the relative abundance of Marinifilacea (p = 0.006), Rikenellacea (p = 0.005), Desulfovibrionaceae (p = 0.045), Tannerellaceae (p = 0.038), Ruminococcaceae (p = 0.003), Clostridia (p = 0.027), and Mycoplasmataceae (p = 0.0009) was significantly increased at the family level in the gut of TLR2-KO colitis mice. In addition, microbiome diversity-transcriptome collaboration analysis highlighted that the relative abundance of Marinifilaceae was negatively linked to the expression of cell cycle signaling-related genes (p values were all less than 0.001).

Conclusion: Based on these findings, we concluded that TLR2-KO exacerbates DSS-triggered intestinal injury by mitigating cell cycle signaling in a Marinifilaceae-dependent manner.

Keywords

Marinifilaceae; cell cycle; dextran sulfate sodium; toll-like receptor 2; ulcerative colitis.

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