ADAMTS8 Promotes Cardiac Fibrosis Partly Through Activating EGFR Dependent Pathway

Zha, Yafang; Li, Yanyan; Ge, Zhuowang; Wang, Jian; Jiao, Yuchen; Zhang, Jiayan; Zhang, Song

doi:10.3389/fcvm.2022.797137

Cited by 13 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Signaling pathways include cytokine signaling in immune system [48], extracellular matrix organization [49], diseases of metabolism [50], hemostasis [51], innate immune system [52], metabolism of lipids [53] [87], CES1 [88], CYP19A1 [89], PLAC8 [90], CD36 [91], GIPR (gastric inhibitory polypeptide receptor) [92], ARG1 [93], MSR1 [94], DOCK2 [95], S1PR1 [96], OXTR (oxytocin receptor) [97], F11R [98], LEPR (leptin receptor) [99], AR (androgen receptor) [100], DKK3 [101], FOXO1 [102], PIK3CB [103], WWP1 [104], PHIP (pleckstrin homology domain interacting protein) [105], MPZL3 [106], FBXO2 [107], GUCY2C [108], ADRA2A [109], CHRNA5 [110], GLP2R [111], SDC3 [112], NFAT5 [113], PON2 [114], PRNP (prion protein) [115], DGKE (diacylglycerol kinase epsilon) [116], ARHGAP21 [117], COQ2 [118], EPHX2 [119] and FAM3C [120] were observed to be associated with the progression of obesity. Vargas-Alarcón et al [ [133], Jiang et al [134], Yu et al [135], Jiang et al [136], Huang et al [137], Scuruchi et al [138], Wang et al [139], Ibrahim et al [140], Zha et al …”

Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems and cancer. The specific mechanism of PCOS and its complications remains unclear. The aim of this study was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of PCOS and its complications. The next generation squancing (NGS) datset GSE199225 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. A protein-protein interaction (PPI) network was constructed and module analysis was performed using HiPPIE and cytoscape. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed for research. The expression of the hub genes was validated using receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs in total, including 478 up regulated genes and 479 down regulated gene. GO and REACTOME illustrated that DEGs in PCOS were significantly enriched in regulation of molecular function, developmental process, interferon signaling and platelet activation, signaling and aggregation. Finally, through analyzing the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN and TCF4 by the Cytoscape software. This study uses a series of bioinformatics technologies to obtain hug genes and key pathways related to PCOS and its complications. These analysis results provide us with novel ideas for finding biomarkers and treatment methods for PCOS and its complications.

show abstract

Section: Discussionmentioning

confidence: 99%

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Vastrad¹,

Vastrad²

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This study found that ADAMTS8 was upregulated in the myocardium of HF rats and ADAMTS8 overexpression counteracted the anti-inflammatory and antifibrotic effects of Yinxin granules. A recent study showed that ADAMTS8 partially promotes cardiac fibrosis by activating epidermal growth factor receptor-dependent pathways, 31) which provides insight into the function of ADAMTS8 in the myocardium. To date, the tumor-suppressive role of ADAMTS 8 has been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Yixin Granules Reduce Myocardial Inflammation and Fibrosis in Rats with Heart Failure by Inhibiting the Expression of ADAMTS8

Wang

Yao

et al. 2023

Int. Heart J.

View full text Add to dashboard Cite

Yixin granules are medications modified from a Chinese prescription (Sheng Xian Tang) that has been used to alleviate shortness of breath. ADAM metallopeptidase with thrombospondin type 1 motif 8 (ADAMTS8) is upregulated in the myocardium of patients with dilated cardiomyopathy. Its high expression is associated with tumor necrosis factor (TNF)-α and myocardial fibrosis. This study aimed to explore the effect of Yixin granules on heart failure (HF) in rats and whether this effect is correlated with ADAMTS8 to provide new ideas for the treatment of HF.HF rat models were established by ligation of the left anterior descending coronary artery. Model rats were injected with adeno-associated virus vectors for the overexpression of ADAMTS8 and/or treated with Yixin granules for 4 weeks. Hematoxylin-eosin and Masson staining were used to detect myocardial injury and fibrosis, respectively. Reverse transcription polymerase chain reaction, western blotting, and/or enzyme-linked immunosorbent assay were used to detect the expression of ADAMTS8, TNF-α, interleukin (IL)-1β, IL-6, collagen I, collagen III, and α-smooth muscle actin in myocardium. The myocardial infarction area of rats was measured using 2,3,5-triphenyltetrazolium chloride staining.ADAMTS8 was upregulated in the myocardium of HF rats. Yixin granule treatment improved left ventricular contractility and reduced ADAMTS8 expression, myocardial injury, inflammation, and fibrosis in HF rats. ADAMTS8 overexpression aggravated myocardial injury, inflammation, and fibrosis. Moreover, ADAMTS8 overexpression counteracted the cardioprotective effects of Yixin granules.Yixin granules may reduce myocardial inflammation and fibrosis in HF rats by inhibiting the expression of ADAMTS8.

show abstract

“…In our dataset, three different variants with uncertain significance have been identified in genes coding for MMPs (MMP24, ADAMTSL5, ADAMTSL8). ADAMTS8 expression was strongly increased in DCM, while in vitro studies evidenced its role into the activation of cardiac fibroblasts [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy

et al. 2022

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM.

show abstract

ADAMTS8 Promotes Cardiac Fibrosis Partly Through Activating EGFR Dependent Pathway

Cited by 13 publications

References 44 publications

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

Yixin Granules Reduce Myocardial Inflammation and Fibrosis in Rats with Heart Failure by Inhibiting the Expression of ADAMTS8

Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy

Contact Info

Product

Resources

About