Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases DOI Creative Commons
Juanjuan Han, C Wang, Haolin Yang

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 514 - 514

Опубликована: Апрель 24, 2024

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is key regulator in the expression genes multitude biological processes. m6A composed 0.1–0.4% adenylate residues, especially at beginning 3′-UTR near translation stop codon. The can be classified into three types, namely “writer”, “reader”, “eraser”. Studies have shown epigenetic modulation influences mRNA processing, nuclear export, translation, splicing. Regulated cell death (RCD) autonomous orderly cells under genetic control to maintain stability internal environment. Moreover, distorted RCDs are widely used influence course various receiving increasing attention from researchers. past few evidence indicated regulate gene thus different RCD processes, which central role etiology evolution MSDs. currently confirmed autophagy-dependent death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic NETotic oxeiptosis. m6A–RCD axis inflammatory response chondrocytes invasive migratory MM bone remodeling capacity, thereby influencing development This review gives complete overview regulatory functions across muscle, bone, cartilage. addition, we also discuss advances by m6A-targeted factors explore clinical application prospects therapies targeting MSD prevention treatment. These may provide new ideas directions for understanding pathophysiological mechanism MSDs treatment these diseases.

Язык: Английский

METTL3-deficiency Suppresses Neural Apoptosis to Induce Protective Effects in Cerebral I/R Injury via Inhibiting RNA m6A Modifications: A Pre-clinical and Pilot Study DOI
Gang Huang,

Yuda Qiu,

Yafei Fan

и другие.

Neurochemical Research, Год журнала: 2023, Номер 49(1), С. 85 - 98

Опубликована: Авг. 23, 2023

Язык: Английский

Процитировано

9
Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice DOI
Miao Fang, Jie Yao, Haifeng Zhang

и другие.

Clinical & Experimental Immunology, Год журнала: 2024, Номер 217(1), С. 57 - 77

Опубликована: Март 20, 2024

Abstract The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress gastric colorectal cancer (CRC). However, its underlying mechanism regulating intestinal inflammation remains unclear poorly investigated. First, characteristics Mettl3 expression inflammatory bowel diseases (IBD) patients were examined. Afterward, we generated mice line with epithelial cells (IECs)-specific deletion verified by various experiments. We continuously recorded compared physiological status including survival rate etc. between two groups. Subsequently, took advantage staining assays to analyze mucosal damage immune infiltration Mettl3WT Mettl3KO primary IECs. Bulk RNA sequencing was used pursuit differential genes (DEGs) associated signaling pathways after losing Mettl3. Pyroptosis-related proteins determine whether cell death caused pyroptosis. Eventually, CyTOF performed probe difference CD45+ cells, especially CD3e+ T-cell clusters In IBD patients, highly expressed inner-nucleus IECs while significantly decreased upon acute inflammation. IECs-specific KO triggered wasting phenotype developed spontaneous colitis. rate, body weight, length observed from 2 8 weeks lower than mice. degree even more serious their WT littermate. demonstrated that DEGs dramatically enriched NOD-signaling due loss colonic epithelium prone pyroptosis revealed T have altered Mettl3KO. Furthermore, there abnormal proliferation CD4+ markedly exhaustion CD8 + severe is located declined when occurs. prevented developing

Язык: Английский

Процитировано

3
Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification DOI
Zhiyong Li, Zheng-gang Chen, Jun Peng

и другие.

Journal of Neurogenetics, Год журнала: 2023, Номер 37(3), С. 103 - 114

Опубликована: Июль 3, 2023

AbstractIschemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve plasticity promote repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized co-cultured with microglia. We found that increased NRF2 expression in oxygen–glucose deprivation/reoxygenation LPS-induced microglia converted M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. reduced m6A methylation modification of nuclear factor erythroid 2-related 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, damage neurons caused by microglia's inflammatory response. Finally, changes polarization neuron FTO knockdown NSE-Exos attenuated overexpression These findings revealed promotes microglial transferring FTO, thereby resulting neuroprotective effects.Keywords: NSC-Exosm6AFTONRF2 Author contributionsConception manuscript: Zhiyong Li, Zhenggang Chen, Jun Peng. Manuscript design writing: Li. reviewing editing: All authors read agreed final version manuscript.Disclosure statementNo conflict interest was reported author(s).Data availability statementData sharing not applicable article as no datasets generated or analysed during current study.Additional informationFundingThis work supported High-level Talents Project Hainan Natural Science Foundation [822RC865] Cerebrovascular Disease Clinical Medical Research Center [LCYX202309].

Язык: Английский

Процитировано

8
The roles of METTL3 on autophagy and proliferation of vascular smooth muscle cells are mediated by mTOR rather than by CDK1 DOI Creative Commons

Hanshen Luo,

Xingliang Wu, Bo Huo

и другие.

Cell Division, Год журнала: 2023, Номер 18(1)

Опубликована: Авг. 9, 2023

Abstract Background Aberrant proliferation of vascular smooth muscle cells (VSMCs) is the cause neointima formation followed by injury. Autophagy involved in this pathological process, but its function controversial. Recently, we found that methyltransferase like 3 (METTL3) inhibited VSMC activating autophagosome formation. Moreover, also demonstrated METTL3 reduced levels phosphorylated mammalian target rapamycin (p-mTOR) and cyclin dependent kinase 1 (p-CDK1/CDC2), which were critical for autophagy regulation. However, whether mTOR CDK1 mediated on VSMCs remains unknown. Results We showed activator mTOR, MHY1485 largely reversed effects overexpression proliferation. Rapamycin, inhibitor obviously nullified pro-proliferation knockdown VSMCs. Unexpectedly, did not contribute to impacts migration phenotypic switching On other hand, with deficiency, was METTL3-regulated VSMCs, effect autophagy. Conclusions concluded role

Язык: Английский

Процитировано

7
Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases DOI Creative Commons
Juanjuan Han, C Wang, Haolin Yang

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 514 - 514

Опубликована: Апрель 24, 2024

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is key regulator in the expression genes multitude biological processes. m6A composed 0.1–0.4% adenylate residues, especially at beginning 3′-UTR near translation stop codon. The can be classified into three types, namely “writer”, “reader”, “eraser”. Studies have shown epigenetic modulation influences mRNA processing, nuclear export, translation, splicing. Regulated cell death (RCD) autonomous orderly cells under genetic control to maintain stability internal environment. Moreover, distorted RCDs are widely used influence course various receiving increasing attention from researchers. past few evidence indicated regulate gene thus different RCD processes, which central role etiology evolution MSDs. currently confirmed autophagy-dependent death, apoptosis, necroptosis, pyroptosis, ferroptosis, immunogenic NETotic oxeiptosis. m6A–RCD axis inflammatory response chondrocytes invasive migratory MM bone remodeling capacity, thereby influencing development This review gives complete overview regulatory functions across muscle, bone, cartilage. addition, we also discuss advances by m6A-targeted factors explore clinical application prospects therapies targeting MSD prevention treatment. These may provide new ideas directions for understanding pathophysiological mechanism MSDs treatment these diseases.

Язык: Английский

Процитировано

2