Pathway-based network analyses and candidate genes associated with Kashin-Beck disease

Zhang, Rongqiang; Guo, Hao; Yang, Xiaoli; Zhang, Dandan; Li, Baorong; Li, Zhaofang; Xiong, Yongmin

doi:10.1097/md.0000000000015498

Cited by 11 publications

(12 citation statements)

References 52 publications

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“…GO enrichment analysis demonstrated that the DMGs and DEGs are mainly enriched in biological processes, for instance, regulation of transforming growth factor beta activation, response to growth factor, extracellular matrix organization, positive regulation of cell death and apoptotic signaling pathway. These findings are consistent with the results of the previous studies [ 21 – 23 ]. Guo et al found the expression of transforming growth factor beta was significantly altered in KBD cartilage, suggesting the association of transforming growth factor beta with cartilage repair [ 21 ].…”

Section: Discussionsupporting

confidence: 94%

“…Guo et al found the expression of transforming growth factor beta was significantly altered in KBD cartilage, suggesting the association of transforming growth factor beta with cartilage repair [ 21 ]. Besides, previous studies have shown the KBD-related genes and deoxynivalenol-regulated genes enriched in the cellular response to growth factor stimulus and extracellular matrix organization respectively [ 22 , 23 ]. It is well recognized that apoptosis of chondrocytes plays a vital role in the pathogenesis of KBD.…”

Section: Discussionmentioning

confidence: 99%

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An integrative analysis of DNA methylation and transcriptome showed the dysfunction of MAPK pathway was involved in the damage of human chondrocyte induced by T-2 toxin

Yang

Xiao

Zhang

et al. 2022

BMC Mol and Cell Biol

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Background T-2 toxin is thought to induce the growth plate and articular cartilage damage of Kashin-Beck disease (KBD), an endemic osteochondropathy in China. This study aims to explore the potential underlying mechanism of such toxic effects by integrating DNA methylation and gene expression profiles. Methods In this study, C28/I2 chondrocytes were treated with T-2 toxin (5 ng/mL) for 24 h and 72 h. Global DNA methylation level of chondrocyte was tested by Enzyme-Linked Immuno Sorbent Assay. Genome-wide DNA methylation and expression profiles were detected using Illumina Infinium HumanMethylation850 BeadChip and RNA-seq technique, respectively. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified mainly for two stages including 24 h group versus Control group and 72 h group versus 24 h group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by Metascape. DMGs and DEGs were further validated by Sequenom MassARRAY system and quantitative real-time polymerase chain reaction. Results The global DNA methylation levels of chondrocytes exposed to T-2 toxin were significantly increased (P < 0.05). For 24 h group versus Control group (24 VS C), 189 DEGs and 590 DMGs were identified, and 4 of them were overlapping. For 72 h group versus 24 h group (72 VS 24), 1671 DEGs and 637 DMGs were identified, and 45 of them were overlapping. The enrichment analysis results of DMGs and DEGs both showed that MAPK was the one of the mainly involved signaling pathways in the regulation of chondrocytes after T-2 toxin exposure (DEGs: P24VSc = 1.62 × 10− 7; P72VS24 = 1.20 × 10− 7; DMGs: P24VSc = 0.0056; P72VS24 = 3.80 × 10− 5). Conclusions The findings depicted a landscape of genomic methylation and transcriptome changes of chondrocytes after T-2 toxin exposure and suggested that dysfunction of MAPK pathway may play important roles in the chondrocytes damage induced by T-2 toxin, which could provide new clues for understanding the potential biological mechanism of KBD cartilage damage induced by T-2 toxin.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

An integrative analysis of DNA methylation and transcriptome showed the dysfunction of MAPK pathway was involved in the damage of human chondrocyte induced by T-2 toxin

Yang

Xiao

Zhang

et al. 2022

BMC Mol and Cell Biol

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“…Candidate genes associated with CMT were collected by retrieving the human genetic association studies deposited in PUBMED ( http://www.ncbi.nlm.nih.gov/pubmed/ ). Referring to published studies [ 17 – 19 ], we searched for reports related to CMT with the term (Charcot-Marie-Tooth Disease [MeSH]) and (polymorphism [MeSH] or genotype [MeSH] or alleles [MeSH]) not (neoplasms [MeSH]). Up to 10 November 2019, a total of 674 publications were retrieved for the disorder.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequently, we visualized the PPI network by means of Cytoscape software (version 3.7.1). Furthermore, the Molecular Complex Detection (MCODE) [ 17 , 31 , 32 ] in Cytoscape software was then performed to select appropriate modules of the PPI network to identify the most important MCODE clusters according to clustering scores. The detailed options set as degree cutoff = 2, K-core = 2, node score cutoff = 0.2, and MAX depth = 100.…”

Section: Methodsmentioning

confidence: 99%

“…In order to further explore the pathogenesis of CMT, we constructed a biological process network to explore possible crosstalk among the significant biological processes. Furthermore, we made a PPI network of these CMT-related genes using MCODE [ 16 , 17 ]. This study may provide further useful insights into the molecular mechanisms of CMT based on a systematic bioinformatics analysis and find causative mutations in the heterogeneous group of disorders (hereditary neuropathies) in the era of NGS.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis

Zhong

Luo

et al. 2020

BioMed Research International

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Charcot-Marie-Tooth Disease (CMT) is the most common clinical genetic disease of the peripheral nervous system. Although many studies have focused on elucidating the pathogenesis of CMT, few focuses on achieving a systematic analysis of biology to decode the underlying pathological molecular mechanisms and the mechanism of its disease remains to be elucidated. So our study may provide further useful insights into the molecular mechanisms of CMT based on a systematic bioinformatics analysis. In the current study, by reviewing the literatures deposited in PUBMED, we identified 100 genes genetically related to CMT. Then, the functional features of the CMT-related genes were examined by R software and KOBAS, and the selected biological process crosstalk was visualized with the software Cytoscape. Moreover, CMT specific molecular network analysis was conducted by the Molecular Complex Detection (MCODE) Algorithm. The biological function enrichment analysis suggested that myelin sheath, axon, peripheral nervous system, mitochondrial function, various metabolic processes, and autophagy played important roles in CMT development. Aminoacyl-tRNA biosynthesis, metabolic pathways, and vasopressin-regulated water reabsorption were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in CMT occurrence and development. According to the crosstalk, the biological processes could be roughly divided into a correlative module and two separate modules. MCODE clusters showed that in top 3 clusters, 13 of CMT-related genes were included in the network and 30 candidate genes were discovered which might be potentially related to CMT. The study may help to update the new understanding of the pathogenesis of CMT and expand the potential genes of CMT for further exploration.

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Plasma metabolites and inflammatory proteins profiling predict outcome of Fufang Duzhong Jiangu granules treating Kashin–Beck disease

Deng,

Niu,

Zhang

et al. 2024

Biomedical Chromatography

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To investigate predictive biomarkers that could be used to identify patients’ response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin–Beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Plasma was collected from 12 KBD patients before treatment and 1 month after FDJG treatment. LC–MS and olink proteomics were employed for obtaining plasma metabolomics profiling and inflammatory protein profiles. Patients were classified into responders and non‐responders based on drug efficacy. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict the drug efficacy. The receiver operating characteristic curve was used to evaluate the prediction accuracy of biomarkers. The changes in metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, d‐glutamine and d‐glutamate metabolism, nitrogen metabolism and NF‐kappa B signaling pathway. Three metabolites were identified as potential predictors: N‐undecanoylglycine, β‐aminopropionitrile and PC [18:3(6Z,9Z,12Z)/20:4(8Z,11Z,14Z,17Z)]. For inflammatory protein, interleukin‐8 was identified as a predictive biomarker to detect responders. Combined use of these four biomarkers had high predictive ability (area under the curve = 0.972).

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Pathway-based network analyses and candidate genes associated with Kashin-Beck disease

Abstract: Supplemental Digital Content is available in the text

Cited by 11 publications

References 52 publications

An integrative analysis of DNA methylation and transcriptome showed the dysfunction of MAPK pathway was involved in the damage of human chondrocyte induced by T-2 toxin

An integrative analysis of DNA methylation and transcriptome showed the dysfunction of MAPK pathway was involved in the damage of human chondrocyte induced by T-2 toxin

Identification of Candidate Genes Associated with Charcot-Marie-Tooth Disease by Network and Pathway Analysis

Plasma metabolites and inflammatory proteins profiling predict outcome of Fufang Duzhong Jiangu granules treating Kashin–Beck disease

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