Background: Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause of intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles in the progression of IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification and gut microbiota to influence NPC senescence.
Methods: An IDD rat model was established by lumbar IVD puncture and NPCs were challenged with IL-1β to mimic IVD injury. IDD rats and IL-1β-exposed NPCs were treated with METTL3-interfering lentivirus and the TLR2 agonist Pam3CSK4. Compositional changes in the rat gut microbiota were analyzed and fecal microbiota transplantation procedures were used. NPC senescence, cell cycle, and the expression of senescence-associated secretory phenotype (SASP) factors were assessed. The m6A enrichment of TLR2 and the binding of IGF2BP1 to TLR2 mRNA were examined.
Results: METTL3 and TLR2 were highly expressed in IDD rats. METTL3 silencing attenuated senescent phenotypes and reduced secretion of SASP factors. Pam3CSK4 reversed the beneficial effects of METTL3 silencing on NPC senescence and IVD injury. METTL3 stabilized TLR2 mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. Fecal microbiota from METTL3 silenced IDD rats altered the pathological phenotypes of IDD rats.
Conclusions: These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/gerona/glae150 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe .
Proc Natl Acad Sci U S A
January 2025
Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602.
is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by has not been explored.
View Article and Find Full Text PDFThe efficacy of Lacticaseibacillus paracasei MSMC39-1 and Bifidobacterium animalis TA-1 probiotics in modulating gut microbiota and reducing the risk of the characteristics of metabolic syndrome: A randomized, double-blinded, placebo-controlled study.
PLoS One
January 2025
Center of Excellence in Probiotics, Srinakharinwirot University, Bangkok, Thailand.
Modern treatment, a healthy diet, and physical activity routines lower the risk factors for metabolic syndrome; however, this condition is associated with all-cause and cardiovascular mortality worldwide. This investigation involved a randomized controlled trial, double-blind, parallel study. Fifty-eight participants with risk factors of metabolic syndrome according to the inclusion criteria were randomized into two groups and given probiotics (Lacticaseibacillus paracasei MSMC39-1 and Bifidobacterium animalis TA-1) (n = 31) or a placebo (n = 27).
View Article and Find Full Text PDFAging-induced Alternation in the Gut Microbiota Impairs Host Antibacterial Defense.
Adv Sci (Weinh)
January 2025
Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Older individuals experience increased susceptibility and mortality to bacterial infections, but the underlying etiology remains unclear. Herein, it is shown that aging-associated reduction of commensal Parabacteroides goldsteinii (P. goldsteinii) in both aged mice and humans critically contributes to worse outcomes of bacterial infection.
View Article and Find Full Text PDFPrognostic value of tumor-infiltrating lymphocyte subtypes and microorganisms in triple-negative breast cancer.
J Cancer Res Ther
December 2024
School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.
Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results.
View Article and Find Full Text PDFThe role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.
J Cancer Res Ther
December 2024
Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!