Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation

Dong, Xiaoliang; Yuan, Bin; Yu, Sheng-zhou; Li, He; Pan, Xiaohua; Sun, Jia; Pan, Li-Long

doi:10.1038/s41401-022-00963-x

Cited by 3 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PRMT5 has been shown to regulate transforming growth factor beta (TGF-β)/Smad3-dependent fibrotic gene transcription, potentially through histone methylation crosstalk, and plays a critical role in cardiac fibrosis and dysfunction 45. Similarly, the contribution of PRMT5 to fibrosis has been confirmed in an Adriamycin-induced cardiac fibrosis model 46. These findings suggest that PRMT5 may serve as a critical mediator in regulating TGF-β-stimulated fibroblast activation and tissue fibrosis.…”

Section: Discussionmentioning

confidence: 86%

“…PRMT5 has been reported to regulate T cells through various pathways, including promoting retinoid-related orphan receptor (ROR)-γt activity and adjusting the Klf2-S1pr1 pathway 41 42. Arginine methylation mediated by PRMTs has emerged as a critical mechanism implicated in fibrosis 43–47. Notably, fibroblast-specific deletion of PRMT5 significantly reduced pressure overload-induced cardiac fibrosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc)

Liang,

Wang,

Tian

et al. 2024

Ann Rheum Dis

View full text Add to dashboard Cite

ObjectivesIn the complex panorama of autoimmune diseases, the characterisation of pivotal contributing autoantibodies that are involved in disease progression remains challenging. This study aimed to employ a global antibody profiling strategy to identify novel antibodies and investigate their association with systemic sclerosis (SSc).MethodsWe implemented this strategy by conducting immunoprecipitation (IP) following on-bead digestion with the sera of patients with SSc or healthy donors, using antigen pools derived from cell lysates. The enriched antigen-antibody complex was proceeded with mass spectrometry (MS)-based quantitative proteomics and over-represented by bioinformatics analysis. The candidate antibodies were then orthogonally validated in two independent groups of patients with SSc. Mice were immunised with the target antigen, which was subsequently evaluated by histological examination and RNA sequencing.ResultsThe IP-MS analysis, followed by validation in patients with SSc, revealed a significant elevation in anti-PRMT5 antibodies among patients with SSc. These antibodies exhibited robust diagnostic accuracy in distinguishing SSc from healthy controls and other autoimmune conditions, including systemic lupus erythematosus and Sjögren’s syndrome, with an area under the curve ranging from 0.900 to 0.988. The elevation of anti-PRMT5 antibodies was verified in a subsequent independent group with SSc using an additional method, microarray. Notably, 31.11% of patients with SSc exhibited seropositivity for anti-PRMT5 antibodies. Furthermore, the titres of anti-PRMT5 antibodies demonstrated a correlation with the progression or regression trajectory in SSc. PRMT5 immunisation displayed significant inflammation and fibrosis in both the skin and lungs of mice. This was concomitant with the upregulation of multiple proinflammatory and profibrotic pathways, thereby underscoring a potentially pivotal role of anti-PRMT5 antibodies in SSc.ConclusionsThis study has identified anti-PRMT5 antibodies as a novel biomarker for SSc.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc)

Liang,

Wang,

Tian

et al. 2024

Ann Rheum Dis

View full text Add to dashboard Cite

show abstract

A comprehensive investigation of PRMT5 in the prognosis and ion channel features of lung cancer

Wang,

Chu,

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

The increasing incidence and mortality associated with lung cancer (LC) is a significant global health challenge. The underlying mechanisms contributing to LC remain inadequately understood. However, emerging evidence suggests that the epigenetic modifier protein arginine methyltransferase 5 (PRMT5) plays a complex role in various cellular processes, including DNA repair, gene transcription, and alternative splicing, through its function in catalyzing the symmetric dimethylation of both histone and non-histone proteins. In this study, we examined the functional role of PRMT5 utilizing LC-related datasets (GSE30219, GSE50081, and TCGA LC cohort) through a series of analyses. Our findings revealed that PRMT5 was significantly overexpressed in LC samples compared to normal tissues and was correlated with overall survival and disease-free survival rates. Additionally, PRDM1 was identified as a key protein exhibiting a strong interaction with PRMT5. The prognostic model that integrated PRMT5 with clinical factors demonstrated robust performance in assessing survival outcomes. Elevated levels of PRMT5 were associated with poor prognosis in LC, as evidenced by analyses of the GSE30219, GSE50081, and TCGA-LC datasets. Furthermore, we identified 27 ion channel (IC) genes exhibited a correlation with PRMT5 in lung adenocarcinoma (LUAD), of which 9 genes were identified as statistically significant with KM survival analysis. Strikingly, all of the 9 genes, including LRRC8A, the same as PRMT5, were associated with poor prognosis in LUAD. Our research highlights the potential of PRMT5 as a novel prognostic biomarker and its relationship with IC genes in LC.

show abstract

Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease

Zhang,

Wei,

Jin

et al. 2024

Diabetes Metab J

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) and metabolic disorders stand as formidable challenges that significantly impact the clinical outcomes and living quality for afflicted individuals. An intricate comprehension of the underlying mechanisms is paramount for the development of efficacious therapeutic strategies. Protein arginine methyltransferases (PRMTs), a class of enzymes responsible for the precise regulation of protein methylation, have ascended to pivotal roles and emerged as crucial regulators within the intrinsic pathophysiology of these diseases. Herein, we review recent advancements in research elucidating on the multifaceted involvements of PRMTs in cardiovascular system and metabolic diseases, contributing significantly to deepen our understanding of the pathogenesis and progression of these maladies. In addition, this review provides a comprehensive analysis to unveil the distinctive roles of PRMTs across diverse cell types implicated in cardiovascular and metabolic disorders, which holds great potential to reveal novel therapeutic interventions targeting PRMTs, thus presenting promising perspectives to effectively address the substantial global burden imposed by CVDs and metabolic disorders.

show abstract

Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation

Cited by 3 publications

References 49 publications

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc)

Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc)

A comprehensive investigation of PRMT5 in the prognosis and ion channel features of lung cancer

Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease

Contact Info

Product

Resources

About