Methyltransferase-like 3 represents a prospective target for the diagnosis and treatment of kidney diseases DOI Creative Commons
Bin Song, Xiaolong Wu, Yan Zeng

et al.

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Nov. 14, 2024

Kidney disease is marked by complex pathological mechanisms and significant therapeutic hurdles, resulting in high morbidity mortality rates globally. A deeper understanding of the fundamental processes involved can aid identifying novel targets improving treatment efficacy. Current comprehensive data analyses indicate involvement methyltransferase-like 3 (METTL3) its role RNA N6-methyladenosine methylation various renal pathologies, including acute kidney injury, fibrosis, chronic disease. However, there a paucity thorough reviews that clarify functional METTL3 evaluate importance enhancing outcomes. This review seeks to systematically examine roles, mechanisms, potential clinical applications diseases. The findings presented suggest implicated etiology exacerbation disorders, affecting their onset, progression, malignancy, responsiveness chemotherapeutic agents through regulation specific genetic pathways. In conclusion, this underscores detrimental correlation between diseases, highlighting promise targeting METTL3. Additionally, it offers critical insights for researchers concerning diagnosis, prognosis, strategies conditions.

Language: Английский

A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone DOI Open Access

Ruizhi Tan,

Jian Jia,

Tong Li

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116922 - 116922

Published: June 13, 2024

The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation acetylation offer new perspectives on the pathogenesis treatment of kidney diseases. lncRNAs, a class transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized key regulatory molecules influencing gene expression through diverse mechanisms. They modulate by recruiting or blocking enzymes responsible for adding removing methyl acetyl groups, DNA, N6-methyladenosine (m6A) histone acetylation, subsequently altering chromatin structure accessibility. In diseases acute injury (AKI), chronic disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), renal cell carcinoma (RCC), aberrant patterns DNA/RNA/histone have been associated onset progression, revealing complex interplay lncRNA dynamics. Recent studies highlighted how lncRNAs can impact pathology affecting function genes involved in cycle control, fibrosis, inflammatory responses. This review will separately address roles diseases, particular emphasis elucidating bidirectional effects underlying mechanisms conjunction addition to potential exacerbating renoprotective pathologies. Understanding reciprocal relationships not only shed light molecular underpinnings pathologies but also present avenues therapeutic interventions biomarker development, advancing precision medicine nephrology.

Language: Английский

Citations

9
WTAP and METTL14 regulate the m6A modification of DKK3 in renal tubular epithelial cells of diabetic nephropathy DOI
Kang Fu,

Chenyang Jing,

Jin‐Song Shi

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 738, P. 150524 - 150524

Published: Aug. 9, 2024

Language: Английский

Citations

4
The inhibition of ZC3H13 attenuates G2/M arrest and apoptosis by alleviating NABP1 m6A modification in cisplatin-induced acute kidney injury DOI Creative Commons
Qinghao Sheng,

Qun Yu,

Shangwei Lu

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Feb. 22, 2025

Acute kidney injury (AKI) is a clinical syndrome caused by various etiologies and causes rapid decline in renal function short period of time. The most common internal modification mRNAs the N6-methyladenosine (m6A) modification, which important for controlling gene expressions. However, role m6A AKI largely unknown. Here, we characterized zinc finger CCCH-type containing 13 (ZC3H13), type methyltransferases, cisplatin-induced mouse model cisplatin-treated human proximal tubular epithelial cell line (HK2 cells). ZC3H13 knockdown attenuated G2/M cycle arrest apoptosis HK2 cells. In ZC3H13-overexpressed cells, opposite was true. presence cisplatin, mice with AAV9-mediated silencing exhibited milder arrest, apoptosis, injury. addition, identified nucleic acid binding protein 1 (NABP1) as target ZC3H13, verified knocking down overexpressing Moreover, confirmed that ZC3H13-mediated stabilized NABP1 mRNA discriminated insulin-like growth factor 2 (IGF2BP1). conclusion, promoted enhanced its stability through an IGF2BP1-dependent mechanism. inhibition alleviated affecting expression NABP1. These results show ZC3H13/NABP1 axis promising treatment target.

Language: Английский

Citations

0
RNA Modification in Metabolism DOI Creative Commons
Yadi Liu,

Zhongyan Sun,

Dingkun Gui

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

ABSTRACT Epigenetic regulation in disease development has been witnessed within this decade. RNA methylation is the predominant form of epigenetic regulation, and most prevalent modification N6‐methyladenosine (m 6 A). Recently, emerged as a potential target for treatment. posttranscriptional gene expression that involved both physiological pathological processes. Evidence suggests m A significantly affects metabolism, its abnormal changes have observed variety diseases. Metabolic diseases are series caused by metabolic processes body, common include diabetes mellitus, obesity, nonalcoholic fatty liver disease, etc.; although pathogenesis these differs from each other to current understanding, recent studies suggested pivotal role modulating diseases, A‐based drug on agenda. This paper reviewed understanding hoping provide systematic information those area.

Language: Английский

Citations

0
m6A-mediated regulation of ECA39 promotes renal fibrosis in chronic kidney disease by enhancing glycolysis and epithelial-mesenchymal transition DOI

Ziyuan Tong,

Hainan Zhao, Chen Cui

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: 1872(6), P. 119981 - 119981

Published: May 1, 2025

Language: Английский

Citations

0
METTL3 promotes podocyte pyroptosis in diabetic nephropathy through N 6 -methyladenosine modification of TRIM29 mRNA DOI Creative Commons
Xiaohong Xu, Xiaolin Huang, Ce Zhang

et al.

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: May 5, 2025

Multiple studies have revealed the critical roles of epigenetic modifications in development diabetic nephropathy (DN). Methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA modification podocytes represents a new disease mechanism DN. The tripartite motif-containing (TRIM) family member TRIM29 was reported to promote podocyte pyroptosis by activating nuclear factor-κB/NLR pyrin domain containing (NLRP3) inflammasome pathway. However, whether METTL3-mediated m6A mRNA is involved injury remain unknown. Here, we found that METTL3 upregulated content from kidney tissues mice with streptozotocin-induced DN and hyperglycemia-induced MPC-5 murine podocytes. expression high glucose-treated cells resulted elevated release interleukin (IL)-1β, IL-18, lactate dehydrogenase pyroptosis-associated molecules. Mechanistically, directly target for activate transcription. Moreover, reader YT521-B homology (YTH) YTHDF1 recruited maintain stability mRNA, which contributed significantly increased pyroptosis. Furthermore, potent METTL3-specific inhibitor STM2457 prominently alleviated through attenuating activation NLRP3 inflammasome/pyroptosis pathway mouse model. Our results suggest plays role provides insight METTL3- pyroptosis-targeted strategies treat other diseases.

Language: Английский

Citations

0
Molecular mechanism of ALKBH5‐mediated m6A demethylation regulating lipopolysaccharide‐induced epithelial–mesenchymal transition in sepsis‐induced acute kidney injury DOI Creative Commons

Haihong Zhao,

Chun‐Ling Chen,

Fen‐Fang Chen

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 40(11), P. 985 - 995

Published: Sept. 17, 2024

Abstract This study explored the mechanism by which m6A demethylase ALKBH5 mediates epithelial–mesenchymal transition (EMT) in sepsis‐associated acute kidney injury (SA‐AKI) and AKI‐chronic disease (CKD) transition. HK‐2 cells were stimulated with lipopolysaccharide (LPS) to establish an vitro model of SA‐AKI. expression was reduced through transfection si‐ALKBH5. Cell viability, apoptosis, migration detected CCK‐8 assay, TUNEL staining, Transwell. The levels TNF‐α, IL‐1β, IL‐6 measured enzyme‐linked immunosorbent assay. Quantitative real‐time polymerase chain reaction or Western blotting performed determine expressions ALKBH5, miR‐205‐5p, DDX5, E‐cadherin, α‐SMA. level quantitatively analyzed. pri‐miR‐205 bound DGCR8 m6A‐modified after intervention RNA immunoprecipitation. A dual‐luciferase assay confirmed binding between miR‐205‐5p DDX5. highly expressed LPS‐induced cells. Inhibition increased cell repressed EMT. modification level, thereby promoting increase eventually targeting DDX5 expression. Low overexpression partially abolished inhibitory effect silencing on In conclusion, represses removing upregulate expression, EMT AKI‐CKD

Language: Английский

Citations

3
Heterogeneous nuclear ribonucleoprotein F deficiency in mouse podocyte promotes podocytopathy mediated by methyltransferase-like 14 nuclear translocation resulting in Sirtuin 1 gene inhibition DOI

Min-Chun Liao,

Chao‐Sheng Lo,

Yuchao Pang

et al.

Translational research, Journal Year: 2024, Volume and Issue: 267, P. 1 - 9

Published: Jan. 7, 2024

Language: Английский

Citations

1
The effect of METTL3 on MDM2 impairs cell cycle homeostasis in podocytes during diabetic kidney disease DOI Creative Commons
Han Wu,

Ziyang Yu,

Yi Yang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 17, 2024

Abstract N6-Methyladenosine (m6A) methylation is involved in various pathological processes. Our previous study found abnormal expression of the methyltransferases enzyme METTL3 aging kidney tissues, resulting renal fibrosis and aging. In this study, we aim to elucidate its regulatory mechanisms diabetic disease (DKD) by establishing a conditional knockout model. We observed elevated m6A levels mice with type I diabetes cultured mouse podocytes exposed advanced glycation end-products (AGEs), which could be attributed increased expression. Podocyte-specific knockdown significantly mitigated podocyte injury streptozotocin (STZ)-induced mice, leading reduced urine albuminuria pathology. Mechanistically, induced modification MDM2, triggering subsequent degradation an IGF2BP2 dependent manner. Consequently, regulation induces MDM2 expression, activates Notch signaling pathway, cell cycle re-entry under conditions, releases inflammatory factors, dedifferentiation podocytes. Thus, METTL3-mediated aberrant plays pivotal role conditions. Targeting via potentially effective strategy for DKD treatment.

Language: Английский

Citations

0
Methyltransferase-like 3 represents a prospective target for the diagnosis and treatment of kidney diseases DOI Creative Commons
Bin Song, Xiaolong Wu, Yan Zeng

et al.

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: Nov. 14, 2024

Kidney disease is marked by complex pathological mechanisms and significant therapeutic hurdles, resulting in high morbidity mortality rates globally. A deeper understanding of the fundamental processes involved can aid identifying novel targets improving treatment efficacy. Current comprehensive data analyses indicate involvement methyltransferase-like 3 (METTL3) its role RNA N6-methyladenosine methylation various renal pathologies, including acute kidney injury, fibrosis, chronic disease. However, there a paucity thorough reviews that clarify functional METTL3 evaluate importance enhancing outcomes. This review seeks to systematically examine roles, mechanisms, potential clinical applications diseases. The findings presented suggest implicated etiology exacerbation disorders, affecting their onset, progression, malignancy, responsiveness chemotherapeutic agents through regulation specific genetic pathways. In conclusion, this underscores detrimental correlation between diseases, highlighting promise targeting METTL3. Additionally, it offers critical insights for researchers concerning diagnosis, prognosis, strategies conditions.

Language: Английский

Citations

0