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

Cardiac Remodeling in Heart Failure: Role of Pyroptosis and Its Therapeutic Implications DOI Creative Commons

Ruoning Chai,

Wenjing Xue,

Shuqing Shi

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Апрель 18, 2022

Pyroptosis is a kind of programmed cell death closely related to inflammation. The pathways that mediate pyroptosis can be divided into the Caspase-1-dependent canonical pathway and Caspase4/5/11-dependent non-canonical pathway. most significant difference from other rapidly causes rupture plasma membrane, expansion, dissolution release contents large number inflammatory factors, send pro-inflammatory signals adjacent cells, recruit cells induce responses. Cardiac remodeling basic mechanism heart failure (HF) core pathophysiological research on underlying mechanism. A studies have shown cause cardiac fibrosis, hypertrophy, cardiomyocytes death, myocardial dysfunction, excessive inflammation, remodeling. Therefore, targeting has good prospect in improving HF. In this review, molecular summarized, relationship between HF analyzed in-depth, potential therapy improve adverse discussed, providing some ideas for study

Язык: Английский

Процитировано

43
RNA modification in cardiovascular disease: implications for therapeutic interventions DOI Creative Commons
Cong Wang,

Xuyang Hou,

Qing Guan

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 27, 2023

Abstract Cardiovascular disease (CVD) is the leading cause of death in world, with a high incidence and youth-oriented tendency. RNA modification ubiquitous indispensable cell, maintaining cell homeostasis function by dynamically regulating gene expression. Accumulating evidence has revealed role aberrant expression CVD caused dysregulated modification. In this review, we focus on nine common modifications: N 6 -methyladenosine (m A), 1 5-methylcytosine 5 C), 7 -methylguanosine G), 4 -acetylcytosine (ac pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, modifications U34 tRNA wobble. We summarize key regulators their effects expression, such as splicing, maturation, transport, stability, translation. Then, based classification CVD, mechanisms which occurs progresses through are discussed. Potential therapeutic strategies, therapy, reviewed these mechanisms. Herein, some (such stroke peripheral vascular disease) not included due to limited availability literature. Finally, prospective applications challenges discussed for purpose facilitating clinical Moreover, look forward more studies exploring roles future, there substantial uncultivated areas be explored.

Язык: Английский

Процитировано

28
MetBil as a novel molecular regulator in ischemia‐induced cardiac fibrosis via METTL3‐mediated m6A modification DOI Open Access

Yuting Zhuang,

Tingting Li, Xiaoxi Hu

и другие.

The FASEB Journal, Год журнала: 2023, Номер 37(3)

Опубликована: Фев. 8, 2023

Cardiac fibrosis is a common pathological manifestation in multiple cardiovascular diseases and often results myocardial stiffness cardiac dysfunctions. LncRNA (long noncoding RNA) participates number of pathophysiological processes. However, its role remains unclear. The purpose this study was to investigate the molecular mechanism MetBil regulating fibrosis. Our data showed that METTL3 binding lncRNA (MetBil) significantly increased both fibrotic tissue following infarction (MI) mice fibroblasts (CFs) exposed TGF-β1 (20 ng/mL) or 20% FBS. Overexpression augmented collagen deposition, CF proliferation activation while silencing exhibited opposite effects. Importantly, heterozygous knockout alleviated improved function after MI. RNA pull-down RNA-binding protein immunoprecipitation assay direct downstream target MetBil; consistently, were co-localized nucleus cytoplasm CFs. Interestingly, regulated expression at level, but not mRNA ubiquitin-proteasome pathway. Enforced canceled antifibrotic effects reflected by production, activation. Most notably, m6A-modified fibrosis-regulated genes mediated are profoundly involved regulation reveals as novel regulator promotes via interacting with methylated fibrosis-associated genes, providing new intervening for diseases.

Язык: Английский

Процитировано

23
m6A epitranscriptomic and epigenetic crosstalk in cardiac fibrosis DOI
Zhiyan Liu,

Li-Chan Lin,

Zhenyu Liu

и другие.

Molecular Therapy, Год журнала: 2024, Номер 32(4), С. 878 - 889

Опубликована: Фев. 3, 2024

Язык: Английский

Процитировано

12
WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury DOI Creative Commons
Yuhua Chen,

Tianlin Long,

Junhui Chen

и другие.

International Journal of Surgery, Год журнала: 2024, Номер 110(9), С. 5396 - 5408

Опубликована: Июнь 14, 2024

Background Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, authors explored epigenetic methylation RNA-mediated NLRP3 inflammasome activation Methods Neurological dysfunction, histopathology, associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , flox/flox pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons used vitro to further explore molecular mechanisms action WTAP/YTHDF1 following neural damage. Results The found that m6A levels upregulated at early stage TBI, deletion did not affect function but promoted functional recovery Conditional suppressed neuroinflammation TBI phase: could directly act on mRNA, regulate mRNA level, promote expression neuronal injury. Further investigation YTH domain YTHDF1 bind protein expression. mutation or silencing improved injury, inhibited Caspase-1 activation, decreased IL-1β levels. This effect was mediated via suppression translation, which also reversed stimulative overexpression inflammation. Conclusions Our results indicate participates damage by translation m6A-YTHDF1-dependent manner WTAP/m6A/YTHDF1 downregulation therapeutics viable promising approach preserving can provide support targeted drug development.

Язык: Английский

Процитировано

12
Mesenchymal Stem Cells-Derived Exosomes Alleviate Acute Lung Injury by Inhibiting Alveolar Macrophage Pyroptosis DOI Creative Commons
Peipei Liu, Shengnan Yang,

Xuecheng Shao

и другие.

Stem Cells Translational Medicine, Год журнала: 2024, Номер 13(4), С. 371 - 386

Опубликована: Фев. 13, 2024

Abstract Acute lung injury (ALI) is an important pathological process of acute respiratory distress syndrome, yet there are limited therapies for its treatment. Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to be effective in suppressing inflammation. However, the effects MSCs-Exo on ALI and underlying mechanisms not well elucidated. Our data showed that MSCs-Exo, but derived from MRC-5 cells (MRC-5-Exo), which human fetal fibroblast cells, significantly improved chest imaging, histological observations, alveolocapillary membrane permeability, reduced inflammatory response mice model. According miRNA sequencing proteomic analysis MRC-5-Exo, may inhibit pyroptosis by miRNAs targeting caspase-1-mediated pathway, proteins with immunoregulation functions. Taken together, our study demonstrated were treating inhibiting alveolar macrophages reducing inflammation response. Its mechanism through pyroptosis-targeting immunoregulating delivered MSCs-Exo. Therefore, a new treatment option early stage ALI.

Язык: Английский

Процитировано

11
N6-Methyladenosine RNA Methylation in Cardiovascular Diseases DOI Creative Commons
Chi Liu, Lei Gu,

Wenjuan Deng

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Апрель 29, 2022

N6-methyladenosine (m6A) modification is the most universal and abundant post-transcriptional of eukaryotic RNA occurs mainly at consensus motif RR CH (R = A or G, H A, C, U) in long internal exons, near stop codons, 3′ untranslated region (UTR). “Writers,” “erasers,” “readers” are responsible for occurrence, removal, recognition m6A modification, respectively. Substantial evidence has shown that can exert important functions physiological pathological processes. Cardiovascular diseases (CVDs) a wide array disorders affecting heart vessels, including atherosclerosis (AS), hypertension (HT), ischemia/reperfusion (I/R) injury, myocardial infarction (MI), stroke, cardiac hypertrophy, failure (HF), so on. Despite advances lipid-lowering drugs, antihypertensives, antiplatelet agents, anticoagulation therapy, CVDs still leading cause death worldwide. Recent studies have suggested may contribute to pathogenesis CVDs, providing novel research insight CVDs. Herein, we provide an up-of-date summarization molecular mechanism roles different types At last, propose might be potiential biomarker therapeutic target

Язык: Английский

Процитировано

32
Pyroptosis: A Newly Discovered Therapeutic Target for Ischemia-Reperfusion Injury DOI Creative Commons
Yu Zheng, Xinda Xu, Fanglu Chi

и другие.

Biomolecules, Год журнала: 2022, Номер 12(11), С. 1625 - 1625

Опубликована: Ноя. 3, 2022

Ischemia-reperfusion (I/R) injury, uncommon among patients suffering from myocardial infarction, stroke, or acute kidney can result in cell death and organ dysfunction. Previous studies have shown that different types of death, including apoptosis, necrosis, autophagy, occur during I/R injury. Pyroptosis, which is characterized by membrane pore formation, pro-inflammatory cytokine release, burst, differentiates itself apoptosis necroptosis, has been found to be closely related Therefore, targeting the signaling pathways key regulators pyroptosis may favorable for treatment far adequate at present. This review summarizes current status its connection organs, as well potential strategies it combat

Язык: Английский

Процитировано

30
METTL3-deficiency m6A-dependently degrades MALAT1 to suppress NLRP3-mediated pyroptotic cell death and inflammation in Mycobacterium tuberculosis (H37Ra strain)-infected mouse macrophages DOI
Limei Han,

Nueramina Tieliwaerdi,

Xin Li

и другие.

Tuberculosis, Год журнала: 2024, Номер 146, С. 102502 - 102502

Опубликована: Март 4, 2024

Язык: Английский

Процитировано

6
Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis DOI Creative Commons
Cong Chen, Jie Wang,

Shan Zhang

и другие.

Redox Biology, Год журнала: 2024, Номер 76, С. 103321 - 103321

Опубликована: Авг. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Язык: Английский

Процитировано

6