TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO/IGF2BP2

References

• Faralli A, Bigoni M, Mauro A, Rossi F, Carulli D. Noninvasive strategies to promote functional recovery after stroke. Neural Plast. 2013;2013:854597. doi:10.1155/2013/854597
   PubMed Web of Science ®Google Scholar
• Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of trimethylamine N-Oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients. 2018;10(10):1398. doi:10.3390/nu10101398
   PubMed Web of Science ®Google Scholar
• Vogt NM, Romano KA, Darst BF, et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther. 2018;10(1):124. doi:10.1186/s13195-018-0451-2
   PubMedGoogle Scholar
• Wang QJ, Shen YE, Wang X, et al. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. Aging. 2020;12(1):628–649. doi:10.18632/aging.102645
   PubMedGoogle Scholar
• Chen SJ, Kuo CH, Kuo HC, et al. The gut metabolite trimethylamine N-oxide is associated with parkinson’s disease severity and progression. Mov Disord. 2020;35(11):2115–2116. doi:10.1002/mds.28246
   PubMed Web of Science ®Google Scholar
• Chung SJ, Rim JH, Ji D, et al. Gut microbiota-derived metabolite trimethylamine N-oxide as a biomarker in early Parkinson’s disease. Nutrition. 2021;83:111090. doi:10.1016/j.nut.2020.111090
   PubMed Web of Science ®Google Scholar
• Zhai Q, Wang X, Chen C, et al. Prognostic value of plasma trimethylamine N-oxide levels in patients with acute ischemic stroke. Cell Mol Neurobiol. 2019;39(8):1201–1206. doi:10.1007/s10571-019-00714-3
   PubMed Web of Science ®Google Scholar
• Borozdenko DA, Shmigol TA, Ezdoglian AA, et al. The effect of a new N-hetero cycle derivative on behavior and inflammation against the background of ischemic stroke. Molecules. 2022;27(17):5488. doi:10.3390/molecules27175488
   PubMed Web of Science ®Google Scholar
• Ding R, Li H, Liu Y, et al. Activating cGAS-STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis. J Neuroinflammation. 2022;19(1):137. doi:10.1186/s12974-022-02511-0
   PubMed Web of Science ®Google Scholar
• Liu HD, Li W, Chen ZR, et al. Expression of the NLRP3 inflammasome in cerebral cortex after traumatic brain injury in a rat model. Neurochem Res. 2013;38(10):2072–2083. doi:10.1007/s11064-013-1115-z
   PubMed Web of Science ®Google Scholar
• Guo Z, Yu S, Chen X, Ye R, Zhu W, Liu X. NLRP3 is involved in ischemia/reperfusion injury. CNS Neurol Disord Drug Targets. 2016;15(6):699–712. doi:10.2174/1871527315666160321111829
   PubMed Web of Science ®Google Scholar
• Yang KL, Li WH, Liu YJ, et al. Hydrogen sulfide attenuates neuroinflammation by inhibiting the NLRP3/Caspase-1/GSDMD pathway in retina or brain neuron following rat ischemia/reperfusion. Brain Sci. 2022;12(9):1245. doi:10.3390/brainsci12091245
   PubMed Web of Science ®Google Scholar
• Zhang X, Fu Y, Li H, et al. H3 relaxin inhibits the collagen synthesis via ROS- and P2X7R-mediated NLRP3 inflammasome activation in cardiac fibroblasts under high glucose. J Cell Mol Med. 2018;22(3):1816–1825. doi:10.1111/jcmm.13464
   PubMed Web of Science ®Google Scholar
• Zhang X, Li Y, Yang P, et al. Trimethylamine-N-oxide promotes vascular calcification through activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) inflammasome and NF-κB (Nuclear Factor κB) signals. Arterioscler Thromb Vasc Biol. 2020;40(3):751–765. doi:10.1161/ATVBAHA.119.313414
   PubMed Web of Science ®Google Scholar
• Zhang C, Fu J, Zhou Y. A review in research progress concerning m6A methylation and immunoregulation. Front Immunol. 2019;10:922. doi:10.3389/fimmu.2019.00922
   PubMed Web of Science ®Google Scholar
• Hong K. Emerging function of N6-methyladenosine in cancer. Oncol Lett. 2018;16(5):5519–5524. doi:10.3892/ol.2018.9395
   PubMed Web of Science ®Google Scholar
• Wu F, Cheng W, Zhao F, Tang M, Diao Y, Xu R. Association of N6-methyladenosine with viruses and related diseases. Virol J. 2019;16(1):133. doi:10.1186/s12985-019-1236-3
   PubMed Web of Science ®Google Scholar
• Chen B, Li Y, Song R, Xue C, Xu F. Functions of RNA N6-methyladenosine modification in cancer progression. Mol Biol Rep. 2019;46(2):2567–2575. doi:10.1007/s11033-019-04655-4
   PubMed Web of Science ®Google Scholar
• Tong J, Flavell RA, Li HB. RNA m(6)A modification and its function in diseases. Front Med. 2018;12(4):481–489. doi:10.1007/s11684-018-0654-8
   PubMed Web of Science ®Google Scholar
• Liu J, Harada BT, He C. Regulation of Gene Expression by N(6)-methyladenosine in Cancer. Trends Cell Biol. 2019;29(6):487–499. doi:10.1016/j.tcb.2019.02.008
   PubMed Web of Science ®Google Scholar
• Chokkalla AK, Mehta SL, Kim T, Chelluboina B, Kim J, Vemuganti R. Transient focal ischemia significantly alters the m(6)A epitranscriptomic tagging of RNAs in the brain. Stroke. 2019;50(10):2912–2921. doi:10.1161/STROKEAHA.119.026433
   PubMed Web of Science ®Google Scholar
• Mathiyalagan P, Adamiak M, Mayourian J, et al. FTO-Dependent N(6)-methyladenosine regulates cardiac function during remodeling and repair. Circulation. 2019;139(4):518–532. doi:10.1161/CIRCULATIONAHA.118.033794
   PubMed Web of Science ®Google Scholar
• Xu K, Mo Y, Li D, et al. N(6)-methyladenosine demethylases Alkbh5/Fto regulate cerebral ischemia-reperfusion injury. Ther Adv Chronic Dis. 2020;11:2040622320916024. doi:10.1177/2040622320916024
   Web of Science ®Google Scholar
• Dai N, Rapley J, Angel M, Yanik MF, Blower MD, Avruch J. mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry. Genes Dev. 2011;25(11):1159–1172. doi:10.1101/gad.2042311
   PubMed Web of Science ®Google Scholar
• Ruan DY, Li T, Wang YN, et al. FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis. Oncogene. 2021;40(33):5168–5181. doi:10.1038/s41388-021-01916-0
   PubMed Web of Science ®Google Scholar
• Lee YH, Kang ES, Kim SH, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53(11–12):991–998. doi:10.1007/s10038-008-0341-8
   PubMed Web of Science ®Google Scholar
• Gamboa-Meléndez MA, Huerta-Chagoya A, Moreno-Macías H, et al. Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population. Diabetes. 2012;61(12):3314–3321. doi:10.2337/db11-0550
   PubMed Web of Science ®Google Scholar
• Zhou H, Shen X, Yan C, et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage. Stem Cell Res Ther. 2022;13(1):322. doi:10.1186/s13287-022-03005-9
   PubMed Web of Science ®Google Scholar
• Liu BH, Tu Y, Ni GX, et al. Total flavones of abelmoschus manihot ameliorates podocyte pyroptosis and injury in high glucose conditions by targeting METTL3-Dependent m(6)A modification-mediated NLRP3-inflammasome activation and PTEN/PI3K/Akt signaling. Front Pharmacol. 2021;12:667644. doi:10.3389/fphar.2021.667644
   PubMed Web of Science ®Google Scholar
• Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63. doi:10.1038/nature09922
   PubMed Web of Science ®Google Scholar
• Zhu W, Gregory JC, Org E, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111–124. doi:10.1016/j.cell.2016.02.011
   PubMed Web of Science ®Google Scholar
• Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91. doi:10.1161/01.STR.20.1.84
   PubMed Web of Science ®Google Scholar
• Xu D, Zhao W, Song J, et al. The relationship of large-artery atherothrombotic stroke with plasma trimethylamine N-Oxide level and blood lipid-related indices: a cross-sectional comparative study. Biomed Res Int. 2021;2021:5549796. doi:10.1155/2021/5549796
   PubMed Web of Science ®Google Scholar
• Gong L, Wang H, Zhu X, et al. Nomogram to predict cognitive dysfunction after a minor ischemic stroke in hospitalized-population. Front Aging Neurosci. 2021;13:637363. doi:10.3389/fnagi.2021.637363
   PubMed Web of Science ®Google Scholar
• Li D, Ke Y, Zhan R, et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell. 2018;17(4):e12768. doi:10.1111/acel.12768
   PubMed Web of Science ®Google Scholar
• Su H, Fan S, Zhang L, Qi H. TMAO aggregates neurological damage following ischemic stroke by promoting reactive astrocytosis and glial scar formation via the Smurf2/ALK5 axis. Front Cell Neurosci. 2021;15:569424. doi:10.3389/fncel.2021.569424
   PubMed Web of Science ®Google Scholar
• Pawluk H, Kołodziejska R, Grześk G, et al. Selected mediators of inflammation in patients with acute ischemic stroke. Int J Mol Sci. 2022;23(18):10614. doi:10.3390/ijms231810614
   PubMed Web of Science ®Google Scholar
• Wang N, Yang Y, Qiu B, et al. Correlation of the systemic immune-inflammation index with short- and long-term prognosis after acute ischemic stroke. Aging. 2022;14(16):6567–6578. doi:10.18632/aging.204228
   PubMedGoogle Scholar
• Simats A, Liesz A. Systemic inflammation after stroke: implications for post-stroke comorbidities. EMBO Mol Med. 2022;14(9):e16269. doi:10.15252/emmm.202216269
   PubMed Web of Science ®Google Scholar
• Kim JY, Park J, Chang JY, Kim SH, Lee JE. Inflammation after ischemic stroke: the role of leukocytes and glial cells. Exp Neurobiol. 2016;25(5):241–251. doi:10.5607/en.2016.25.5.241
   PubMed Web of Science ®Google Scholar
• Lai AY, Todd KG. Microglia in cerebral ischemia: molecular actions and interactions. Can J Physiol Pharmacol. 2006;84(1):49–59. doi:10.1139/Y05-143
   PubMed Web of Science ®Google Scholar
• Wood PL. Microglia as a unique cellular target in the treatment of stroke: potential neurotoxic mediators produced by activated microglia. Neurol Res. 1995;17(4):242–248. doi:10.1080/01616412.1995.11740321
   PubMed Web of Science ®Google Scholar
• Xue M, Mikliaeva EI, Casha S, Zygun D, Demchuk A, Yong VW. Improving outcomes of neuroprotection by minocycline: guides from cell culture and intracerebral hemorrhage in mice. Am J Pathol. 2010;176(3):1193–1202. doi:10.2353/ajpath.2010.090361
   PubMed Web of Science ®Google Scholar
• Park SH, Lee YS, Yang HJ, Song GJ. Fluoxetine potentiates phagocytosis and autophagy in microglia. Front Pharmacol. 2021;12:770610. doi:10.3389/fphar.2021.770610
   PubMed Web of Science ®Google Scholar
• de Rivero Vaccari JP, Dietrich WD, Keane RW. Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J Cereb Blood Flow Metab. 2014;34(3):369–375. doi:10.1038/jcbfm.2013.227
   PubMed Web of Science ®Google Scholar
• de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci. 2008;28(13):3404–3414. doi:10.1523/JNEUROSCI.0157-08.2008
   PubMed Web of Science ®Google Scholar
• Zhu H, Jian Z, Zhong Y, et al. Janus kinase inhibition ameliorates ischemic stroke injury and neuroinflammation through reducing NLRP3 inflammasome activation via JAK2/STAT3 pathway inhibition. Front Immunol. 2021;12:714943. doi:10.3389/fimmu.2021.714943
   PubMed Web of Science ®Google Scholar
• Haque ME, Akther M, Jakaria M, Kim IS, Azam S, Choi DK. Targeting the microglial NLRP3 inflammasome and its role in Parkinson’s disease. Mov Disord. 2020;35(1):20–33. doi:10.1002/mds.27874
   PubMed Web of Science ®Google Scholar
• Hanslik KL, Ulland TK. The role of microglia and the Nlrp3 inflammasome in Alzheimer’s disease. Front Neurol. 2020;11:570711. doi:10.3389/fneur.2020.570711
   PubMed Web of Science ®Google Scholar
• Zhang Z, Wang Q, Zhao X, et al. YTHDC1 mitigates ischemic stroke by promoting Akt phosphorylation through destabilizing PTEN mRNA. Cell Death Dis. 2020;11(11):977. doi:10.1038/s41419-020-03186-2
   PubMed Web of Science ®Google Scholar
• Si W, Li Y, Ye S, et al. Methyltransferase 3 mediated miRNA m6A methylation promotes stress granule formation in the early stage of acute ischemic stroke. Front Mol Neurosci. 2020;13:103. doi:10.3389/fnmol.2020.00103
   PubMed Web of Science ®Google Scholar
• Song Z, Qiu L, Hu Z, Liu J, Liu D, Hou D. Evaluation of the obesity genes FTO and MC4R for contribution to the risk of large artery atherosclerotic stroke in a Chinese Population. Obes Facts. 2016;9(5):353–362. doi:10.1159/000448588
   PubMed Web of Science ®Google Scholar
• Huang J, Sun W, Wang Z, et al. FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner. J Exp Clin Cancer Res. 2022;41(1):42. doi:10.1186/s13046-022-02254-z
   PubMed Web of Science ®Google Scholar
• Sun M, Zhang X, Bi F, et al. FTO inhibits epithelial ovarian cancer progression by destabilising SNAI1 mRNA through IGF2BP2. Cancers. 2022;14(21):5218. doi:10.3390/cancers14215218
   PubMed Web of Science ®Google Scholar