C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a mutant dystrophin protein. DMD patients undergo gradual progressive paralysis until death. Chronic glucocorticoid therapy remains one of the main treatments for DMD, despite the significant side effects. However, its mech...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Bioengineered |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21655979.2021.1967029 |
| _version_ | 1798034031030304768 |
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| author | Jie Chen Xinsheng Lai |
| author_facet | Jie Chen Xinsheng Lai |
| author_sort | Jie Chen |
| collection | DOAJ |
| description | Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a mutant dystrophin protein. DMD patients undergo gradual progressive paralysis until death. Chronic glucocorticoid therapy remains one of the main treatments for DMD, despite the significant side effects. However, its mechanisms of action remain largely unknown. We used bioinformatics tools to identify pathogenic genes involved in DMD and glucocorticoid target genes. Two gene expression profiles containing data from DMD patients and healthy controls (GSE38417 and GSE109178) were downloaded for further analysis. Differentially expressed genes (DEGs) between DMD patients and controls were identified using GEO2R, and glucocorticoid target genes were predicted from the Pharmacogenetics and Pharmacogenomics Knowledge Base. Surprisingly, only one gene, CXCL12 (C–X–C motif chemokine ligand 12), was both a glucocorticoid target and a DEG. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, Gene Ontology term enrichment analysis, and gene set enrichment analysis were performed. A protein–protein interaction network was constructed and hub genes identified using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape. Enriched pathways involving the DEGs, including CXCL12, were associated with the immune response and inflammation. Levels of CXCL12 and its receptor CXCR4 (C–X–C motif chemokine receptor 4) were increased in X-linked muscular dystrophy (mdx) mice (DMD models) but became significantly reduced after prednisone treatment. Metformin also reduced the expression of CXCL12 and CXCR4 in mdx mice. In conclusion, the CXCL12–CXCR4 pathway may be a potential target for DMD therapy. |
| first_indexed | 2024-04-11T20:38:34Z |
| format | Article |
| id | doaj.art-1dca640111384bc8a9c1a6c3d212ae70 |
| institution | Directory Open Access Journal |
| issn | 2165-5979 2165-5987 |
| language | English |
| last_indexed | 2024-04-11T20:38:34Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Bioengineered |
| spelling | doaj.art-1dca640111384bc8a9c1a6c3d212ae702022-12-22T04:04:18ZengTaylor & Francis GroupBioengineered2165-59792165-59872021-01-011215428543910.1080/21655979.2021.19670291967029C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophyJie Chen0Xinsheng Lai1School of Life Science, Nanchang UniversitySchool of Life Science, Nanchang UniversityDuchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a mutant dystrophin protein. DMD patients undergo gradual progressive paralysis until death. Chronic glucocorticoid therapy remains one of the main treatments for DMD, despite the significant side effects. However, its mechanisms of action remain largely unknown. We used bioinformatics tools to identify pathogenic genes involved in DMD and glucocorticoid target genes. Two gene expression profiles containing data from DMD patients and healthy controls (GSE38417 and GSE109178) were downloaded for further analysis. Differentially expressed genes (DEGs) between DMD patients and controls were identified using GEO2R, and glucocorticoid target genes were predicted from the Pharmacogenetics and Pharmacogenomics Knowledge Base. Surprisingly, only one gene, CXCL12 (C–X–C motif chemokine ligand 12), was both a glucocorticoid target and a DEG. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, Gene Ontology term enrichment analysis, and gene set enrichment analysis were performed. A protein–protein interaction network was constructed and hub genes identified using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape. Enriched pathways involving the DEGs, including CXCL12, were associated with the immune response and inflammation. Levels of CXCL12 and its receptor CXCR4 (C–X–C motif chemokine receptor 4) were increased in X-linked muscular dystrophy (mdx) mice (DMD models) but became significantly reduced after prednisone treatment. Metformin also reduced the expression of CXCL12 and CXCR4 in mdx mice. In conclusion, the CXCL12–CXCR4 pathway may be a potential target for DMD therapy.http://dx.doi.org/10.1080/21655979.2021.1967029duchenne muscular dystrophybioinformatic analysisdifferentially expressed genescxcl12glucocorticoids |
| spellingShingle | Jie Chen Xinsheng Lai C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy Bioengineered duchenne muscular dystrophy bioinformatic analysis differentially expressed genes cxcl12 glucocorticoids |
| title | C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy |
| title_full | C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy |
| title_fullStr | C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy |
| title_full_unstemmed | C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy |
| title_short | C–X–C motif chemokine ligand 12: a potential therapeutic target in Duchenne muscular dystrophy |
| title_sort | c x c motif chemokine ligand 12 a potential therapeutic target in duchenne muscular dystrophy |
| topic | duchenne muscular dystrophy bioinformatic analysis differentially expressed genes cxcl12 glucocorticoids |
| url | http://dx.doi.org/10.1080/21655979.2021.1967029 |
| work_keys_str_mv | AT jiechen cxcmotifchemokineligand12apotentialtherapeutictargetinduchennemusculardystrophy AT xinshenglai cxcmotifchemokineligand12apotentialtherapeutictargetinduchennemusculardystrophy |