The Role of N6-Methyladenosine in Inflammatory Diseases

Xu, Haojun; Lin, Changjie; Yang, Jinghan; Chen, Xi; Chen, Yingyu; Chen, Jianguo; Guo, Aizhen; Wang, Chaohao

doi:10.1155/2022/9744771

Cited by 6 publications

(5 citation statements)

References 198 publications

(244 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we are surprised to find that inhibition of abnormal expression of m6A methylation levels also promoted the transformation of M1 macrophages induced by LPS to M2 macrophages. In contrast, METTL3 knockdown have been shown to have impaired colon barriers (38,39). To confirm the role of m6A in the colon inflammation, we examined the effects of SAH on Caco2 cells and RAW264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

Li,

Ma,

Wang

et al. 2024

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Colon inflammation is characterized by disturbances in the intestinal microbiota and inflammation. Melatonin (Mel) can improve colon inflammation. However, the underlying mechanism remains unclear. Recent studies suggest that m6A methylation modification may play an important role in inflammatory responses. This study aimed to explore the effects of melatonin and LPS-mediated m6A methylation on colon inflammation. Our study found that melatonin inhibits M1 macrophages, activates M2 macrophages, inhibit the secretion of pro-inflammatory factors, maintain colon homeostasis and improves colon inflammation through MTNR1B. In addition, the increased methylation level of m6A is associated with the occurrence of colon inflammation, and melatonin can also reduce the level of colon methylation to improve colon inflammation. Among them, the main methylated protein METTL3 can be inhibited by melatonin through MTNR1B. In a word, melatonin regulates m6A methylation by improving abnormal METTL3 protein level to reshape the microflora and activate macrophages to improve colon inflammation, mainly through MTNR1B.

show abstract

Section: Discussionmentioning

confidence: 99%

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

Li,

Ma,

Wang

et al. 2024

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…Although some evidence has indicated that m 6 A modification plays an essential role in inflammation and inflammatory diseases (Cui et al, 2022;Xu et al, 2022), the intrinsic principles remain unclear. By analyzing data obtained from the Gene Expression Omnibus (GEO) dataset (GSE13887/137268/69063/97779/166388/208303, Appendix Table S1), we found that the expression of WTAP is commonly upregulated in patients with SLE, asthma, sepsis, rheumatoid arthritis, psoriasis, or Crohn's disease To verify the abovementioned observations, THP-1 cells were treated with the Toll-like receptor 4 (TLR4) agonist LPS, an ideal reagent to activate the inflammatory signalling cascade in vivo (Triantafilou & Triantafilou, 2002).…”

Section: Hyperinflammation Is Accompanied By Elevated Wtap Levels In ...mentioning

confidence: 99%

WTAP, transcriptionally regulated by p65, promotes inflammation through m⁶A modification and phase separation

Ge,

Chen,

Ling

et al. 2023

Preprint

View full text Add to dashboard Cite

Emerging evidence has linked dysregulation ofN6-methyladenosine (m6A) to inflammation and inflammatory diseases, but the underlying mechanism remains lacking. Here, we found that high m6A modification in a variety of hyperinflammatory states is p65-dependent, because WTAP, a key component of the writer complex, is transcriptionally regulated by p65 and its overexpression can lead to higher m6A modification. Mechanistically, upregulated WTAP is more prone to phase separation to facilitate the aggregation of “writer” complex to nuclear speckles and the deposition of m6A marks onto transcriptionally active inflammatory transcripts, thereby accelerating proinflammatory response. Furthermore, myeloid deficiency of WTAP attenuates the severity of LPS-induced sepsis and DSS-induced IBD. Thus, the proinflammatory effect of WTAP is a general risk-increasing mechanism, and interrupting the assembly of m6A writer complex by targeting the phase separation of WTAP to reduce the global m6A level may be a potential and promising therapeutic strategy for alleviating hyperinflammation.

show abstract

“…m 6 A facilitates the progression of several inflammatory diseases, such as non-alcoholic fatty liver disease, autoimmune diseases, and infections [ 17 – 20 ]. Evidently, global m 6 A levels are significantly increased in alveolar epithelial cells, mediated by the upregulation of METTL3, which is closely associated with ALI [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner

Cao,

Chen,

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Acute lung injury (ALI) as well as its more severe form, acute respiratory distress syndrome (ARDS), frequently leads to an uncontrolled inflammatory response. N6-methyladenosine (m6A) modification was associated with the progression of several inflammatory diseases. However, the role of methyltransferase-like 14 (METTL14)-mediated m6A methylation in ALI/ARDS remains unclear. Here, we reported an increase in overall expression levels of m6A and METTL14 in circulating monocyte-derived macrophages recruited to the lung following ALI, which is correlated with the severity of lung injury. We further demonstrated the critical function of METTL14 in activating NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in vitro and in mouse models of ALI/ARDS, and validated NLRP3 as the downstream target of METTL14 by the m6A RNA immunoprecipitation (MeRIP) and RIP assays. Mechanistically, METTL14-methylated NLRP3 transcripts were subsequently recognized by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6A reader, which stabilized NLRP3 mRNA. Furthermore, we observed that IGF2BP2 knockdown diminished LPS-induced ALI in mice by downregulating NLRP3 expression. In summation, our study revealed that the molecular mechanism underlying the pathogenesis of ALI/ARDS involves METTL14-mediated activation of NLRP3 inflammasome in an IGF2BP2 dependent manner, thereby demonstrating the potential of METTL14 and IGF2BP2 as promising biomarkers and therapeutic targets for ALI/ARDS treatment.

show abstract

The Role of N6-Methyladenosine in Inflammatory Diseases

Cited by 6 publications

References 198 publications

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

WTAP, transcriptionally regulated by p65, promotes inflammation through m⁶A modification and phase separation

METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner

Contact Info

Product

Resources

About

The Role of N6-Methyladenosine in Inflammatory Diseases

Cited by 6 publications

References 198 publications

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation

WTAP, transcriptionally regulated by p65, promotes inflammation through m6A modification and phase separation

METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner

Contact Info

Product

Resources

About

WTAP, transcriptionally regulated by p65, promotes inflammation through m⁶A modification and phase separation