PMID- 34424816
OWN - NLM
STAT- MEDLINE
DCOM- 20211222
LR  - 20220204
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Dec
TI  - C-X-C motif chemokine ligand 12: a potential therapeutic target in Duchenne 
      muscular dystrophy.
PG  - 5428-5439
LID - 10.1080/21655979.2021.1967029 [doi]
AB  - 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.
FAU - Lai, Xinsheng
AU  - Lai X
AUID- ORCID: 0000-0002-6044-7811
AD  - School of Life Science, Nanchang University, Nanchang, Jiangxi, China.
AD  - Laboratory of Synaptic Development and Plasticity, Institute of Life Science, 
      Nanchang University, Nanchang, Jiangxi, China.
FAU - Chen, Jie
AU  - Chen J
AD  - School of Life Science, Nanchang University, Nanchang, Jiangxi, China.
AD  - Laboratory of Synaptic Development and Plasticity, Institute of Life Science, 
      Nanchang University, Nanchang, Jiangxi, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Animals
MH  - *Chemokine CXCL12/genetics/metabolism
MH  - Computational Biology
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred mdx/*genetics
MH  - *Muscular Dystrophy, Duchenne/genetics/metabolism
MH  - Receptors, CXCR4/genetics/metabolism
MH  - Transcriptome/drug effects/genetics
PMC - PMC8806931
OTO - NOTNLM
OT  - Duchenne muscular dystrophy
OT  - bioinformatic analysis
OT  - cxcl12
OT  - differentially expressed genes
OT  - glucocorticoids
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/24 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/08/23
CRDT- 2021/08/23 17:31
PHST- 2021/08/23 17:31 [entrez]
PHST- 2021/08/24 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/08/23 00:00 [pmc-release]
AID - 1967029 [pii]
AID - 10.1080/21655979.2021.1967029 [doi]
PST - ppublish
SO  - Bioengineered. 2021 Dec;12(1):5428-5439. doi: 10.1080/21655979.2021.1967029.