SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy DOI Creative Commons

Yu Ren,

Yun Wu,

Wenshuai He

et al.

Open Medicine, Journal Year: 2023, Volume and Issue: 18(1)

Published: Jan. 1, 2023

Heart failure (HF) is a major global cause of morbidity and mortality. This study aimed to elucidate the role secreted protein acidic rich in cysteine-related modular calcium-binding 2 (SMOC2) HF development its underlying mechanism. Using rat model, SMOC2 expression was examined then knocked down via transfection assess impact on cardiac function damage. The also evaluated effects knockdown autophagy-related molecules transforming growth factor beta 1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway. Intraperitoneal injection TGF-β agonist (SRI-011381) into model performed explore SMOC2-TGF-β1/Smad3 pathway relationship. elevated rats, while downregulation improved reversed alterations LC3-II/I ratio, Beclin-1, p62 levels rats. Through transmission electron microscope, we observed that restored autophagosome levels. Furthermore, inhibited TGF-β1/Smad3 pathway, which counteracted by SRI-011381. In conclusion, inhibits modulating signaling-mediated autophagy, suggesting potential as therapeutic target for HF.

Language: Английский

Cardiac protection of wogonin in mice with pulmonary fibrosis by regulating Sirt1/ γ-H2AX pathway DOI Creative Commons
Libo Wang,

Fei Lin,

Runran Miao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Background Clinical evidence suggests that pulmonary fibrosis (PF) and heart failure (HF) often co-exist; however, the specific impact of PF on HF remains underexplored. This gap in understanding complicates management treatment patients with PF. Objectives To investigate effects cardiac function myocardial using a mouse model evaluate therapeutic potential wogonin, flavonoid compound known for its anti-PF properties. Methods A was established via intratracheal administration bleomycin (BLM). Starting day 8 post-BLM treatment, wogonin (50 mg/kg) intraperitoneally administered every 2 days weeks. Cardiac assessed echocardiography, while evaluated through Masson staining. In vitro , H9C2 cardiomyocytes were exposed to CoCl or H O 24 h without (20 μM) treatment. Apoptosis DNA damage markers analysed immunofluorescence, immunoblotting, Comet assay. The interaction between Sirt1 examined biotin-affinity pulldown assays molecular docking simulations. Results Mice exhibited significant dysfunction fibrosis. Wogonin markedly improved ejection fraction attenuated mice. Mechanistic studies revealed alleviated cardiomyocyte apoptosis by upregulating downregulating γ-H2AX expression. Docking simulations predicted forms stable complex hydrogen-bonding hydrophobic interactions, which further validated assays. Conclusion exerts protective against mice modulating Sirt1/γ-H2AX-mediated pathways reduce apoptosis. These findings suggest as agent managing associated

Language: Английский

Citations

0
Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function DOI Creative Commons
Xiaogang Li, Ruixuan Li,

Nana You

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: May 18, 2022

We aimed to investigate the effect and mechanism of butyric acid on rat myocardial fibrosis (MF). 16S rRNA sequencing was used analyze gut microbiota characteristics Sham group MF group. HPLC applied measure in feces serum. In vitro, macrophages RMa-bm were stimulated with LPS IL-4, respectively, then butyrate added study influences M1/M2 polarization mitochondrial function macrophages. The fibroblasts co-cultured explore fibroblasts. addition, rats fed diet. Compared group, collagen deposition increased, serious. abundance Desulfovibrionaceae Helicobacteraceae increased compared Gut epithelial cells destroyed content decreased. Butyrate inhibited M1 promoted M2. Furthermore, may promote recovery by regulating After adding butyrate, cell proliferation ability decreased, aging apoptosis which indicated that activity. Moreover, could protect mitochondria improve symptoms MF. Butyric ameliorated promoting function.

Language: Английский

Citations

15
Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti‐cardiac fibrosis activity DOI
Yuxuan Yang, Jia Guo,

Chuang Liu

et al.

Archiv der Pharmazie, Journal Year: 2024, Volume and Issue: 357(8)

Published: April 28, 2024

Abstract Three series of N ‐{[4‐([1,2,4]triazolo[1,5‐ α ]pyridin‐6‐yl)‐5‐(6‐methylpyridin‐2‐yl)‐1 H ‐imidazol‐2‐yl]methyl}acetamides ( 14a – d , 15a n and 16a f ) were synthesized evaluated for activin receptor‐like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 activity selectivity. half maximal concentration (IC 50 phosphorylation 16f (9.1 nM), the most potent compound, was 2.7 times that clinical candidate EW‐7197 (vactosertib) 14 LY‐2157299. selectivity index against p38α mitogen‐activated protein >109, which much higher than positive controls (EW‐7197: >41, LY‐2157299: 4). Furthermore, a molecular docking study provided interaction modes between ALK5. Compounds 14c 14d effectively inhibited expression α‐smooth muscle actin (α‐SMA), collagen I, tissue inhibitor metalloproteinase 1 (TIMP‐1)/matrix 13 (MMP‐13) transforming growth factor‐β‐induced human umbilical vein endothelial cells. especially at low concentrations, suggests these could inhibit myocardial cell fibrosis. are potential preclinical candidates treatment cardiac

Language: Английский

Citations

3
EPHB2 Knockdown Mitigated Myocardial Infarction by Inhibiting MAPK Signaling DOI
Xiao‐Yan Jiang, Wenhua Wang, Haofei Kang

et al.

Advanced Biology, Journal Year: 2024, Volume and Issue: 8(9)

Published: July 2, 2024

Myocardial infarction (MI) is a common type of cardiovascular disease. The incidence ventricular remodeling dysplasia and heart failure increases significantly after MI. objective this study to investigate whether erythropoietin hepatocellular receptor B2 (EPHB2) can regulate myocardial injury MI explore its regulatory pathways. EPHB2 overexpressed in the tissues mice. downregulation alleviates cardiac function damage Knockdown MI-induced tissue inflammation apoptosis, fibrosis knockdown inhibits activation mitogen activated kinase-like protein (MAPK) pathway Moreover, overexpression promotes phosphorylation MAPK pathway-related protein, which be reversed by MAPK-IN-1 (an inhibitor) treatment. In conclusion, silencing mitigate inhibiting signaling mice, suggesting that targeting promising therapeutic target for injury.

Language: Английский

Citations

3
PiRNA CFAPIR inhibits cardiac fibrosis by regulating the muscleblind-like protein MBNL2 DOI

Lin Lv,

Keying Yuan,

Jiahao Li

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(8), P. 167456 - 167456

Published: Aug. 8, 2024

Language: Английский

Citations

3
Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases DOI Creative Commons
Sumra Komal, Yuan Gao,

Zhi-Mo Wang

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1353 - 1353

Published: Oct. 10, 2024

Myocardial fibroblasts play a crucial role in heart structure and function. In recent years, significant progress has been made understanding the epigenetic regulation of myocardial fibroblasts, which is essential for cardiac development, homeostasis, disease progression. healthy hearts, (CFs) synthesizing extracellular matrix (ECM) when dormant state. However, under pathological environmental stress, CFs transform into activated known as myofibroblasts. These myofibroblasts produce an excess ECM, promotes fibrosis. Although multiple molecular mechanisms are associated with CF activation dysfunction, emerging evidence highlights involvement this process. Epigenetics refers to heritable changes gene expression that occur without altering DNA sequence. have emerged key regulators fibroblast This review focuses on advancements emphasizes impact modifications activation. Furthermore, we present perspectives prospects future research their implications fibroblasts.

Language: Английский

Citations

3
NAT10‐mediated RNA ac4C acetylation contributes to the myocardial infarction‐induced cardiac fibrosis DOI Creative Commons
Jun Li,

Feierkaiti Yushanjiang,

Zhao Fang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(21)

Published: Nov. 1, 2024

Cardiac fibrosis is featured cardiac fibroblast activation and extracellular matrix accumulation. Ac4C acetylation an important epigenetic regulation of RNAs that has been recently discovered, it solely carried out by NAT10, the exclusive enzyme used for modification. However, potential regulatory mechanisms ac4C in myocardial following infarction remain poorly understood. In our study, we activated fibroblasts vitro using TGF-β1 (20 ng/mL), followed establishing a mouse model to evaluate impact NAT10 on collagen synthesis proliferation. We utilized inhibitor, Remodelin, attenuate capacity NAT10. tissues chronic mice cultured (CFs) response treatment, there was elevation levels expression. This increase facilitated proliferation, accumulation collagens, as well fibroblast-to-myofibroblast transition. Through administration effectively reduced inhibiting NAT10's ability acetylate mRNA. Inhibition resulted changes collagen-related gene expression levels. Mechanistically, found upregulates modification BCL-XL mRNA enhances stability mRNA, thereby upregulating its protein expression, Caspase3 blocking apoptosis CFs. Therefore, crucial involvement NAT10-mediated significant progression, affording promising molecular targets treatment relevant diseases.

Language: Английский

Citations

3
Biomarcadores Potenciais na Fibrose Miocárdica: Uma Análise Bioinformática DOI Creative Commons
Wang Cheng-Mei, Gang Luo, Ping Liu

et al.

Arquivos Brasileiros de Cardiologia, Journal Year: 2024, Volume and Issue: 121(12)

Published: Jan. 1, 2024

Resumo Fundamento A fibrose miocárdica (FM) ocorre durante o início e a progressão da doença cardiovascular, diagnóstico precoce FM é benéfico para melhorar função cardíaca, mas há uma falta de pesquisa sobre biomarcadores precoces FM. Objetivos Utilizando técnicas bioinformática, identificamos potenciais Métodos Os conjuntos dados relacionados à foram obtidos do banco Gene Expression Omnibus (GEO). Após processamento dos dados, genes diferencialmente expressos rastreados. Genes enriquecidos e, subsequentemente, interação proteína-proteína (PPI) foi realizado analisar os diferenciais. miRNAs associados fatores transcrição previstos esses centrais. Finalmente, validação ROC realizada nos centrais determinar sua especificidade sensibilidade como biomarcadores. O nível significância adotado 5% (p < 0,05). Resultados Um total 91 identificados, análise PPI produziu 31 enriquecimento mostrou que apoptose, colágeno, matriz extracelular, adesão celular inflamação estavam envolvidos na Cento quarenta dois identificados. JUN, NF-κB1, SP1, RELA, SRF STAT3 maioria alvos principais. Por fim, IL11, GADD45B, GDF5, NOX4, IGFBP3, ACTC1, MYOZ2 ITGB8 tiveram maior precisão diagnóstica predição com base curva ROC. Conclusão Oito genes, ITGB8, podem servir candidatos Processos apoptose celular, síntese proteína formação estão implicados no desenvolvimento

Citations

3
A comprehensive study on the impact of Ligustrum vicaryi L. fruit polysaccharide on myocardial fibrosis through animal experiments, network pharmacology and molecular docking DOI Creative Commons
Shuling Liu, Meifang Liu, Jianan Wang

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 20, 2025

Myocardial fibrosis (MF) is a prevalent pathological condition associated with various heart diseases, such as failure and arrhythmias, which disrupt electrical signals reduce pumping efficiency. This research explored the therapeutic effects potential mechanisms of Ligustrum vicaryi L. fruit polysaccharide (LVFP) on MF. In vivo experiments, including markers assay, echocardiography, HE staining, Sirius red Masson's trichrome were performed to evaluate efficacy LVFP in treating isoproterenol (ISO)-induced We utilized PharmMapper database identify targets LVFP, aiming explore targets. Additionally, we obtained MF-related from GeneCards database. Venny, bioinformatics tool, intersection between those related STRING construct protein interaction network for overlapping identified key MF through cytoHubba analysis. conducted Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis also examined using molecular docking techniques. significantly inhibited biomarker hydroxyproline (HYP) decreased myocardial level shown by weight tibia length (HW/TL) measurement when compared ISO-treated mice. it increased ejection fraction (EF) fractional shortening (FS) levels. showed collagen levels mice histological quantification cardiac fibrosis. Based monosaccharide structures 413 identified, 67 Analysis indicated that 9 hub genes (AKT1, HSP90AA1, SRC, GSK3β, VEGFR2, RHOA, ENO1, PKM, IL-2) play roles treatment participating signaling pathways prostate cancer, lipid atherosclerosis, insulin resistance. Molecular results exhibited strong binding VEGFR2 (-8.65 kcal/mol), AKT1 (-7.36 kcal/mol) GSK3β (-7.68 kcal/mol). shows promise agent MF, primarily regulation These findings provide novel insights utilizing LVFP.

Language: Английский

Citations

0
Epigenetic alterations of TGFβ and its main canonical signaling mediators in the context of cardiac fibrosis DOI

Luis Algeciras,

Ana Palanca, David Maestro

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2021, Volume and Issue: 159, P. 38 - 47

Published: June 10, 2021

Language: Английский

Citations

19