miRNAmRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatininduced acute kidney injury identifies roles for miR210/Serpine1 and miR378/Fos in regulating inflammation.
Mol Med Rep
; 20(2): 1509-1522, 2019 Aug.
Article
in En
| MEDLINE
| ID: mdl-31257474
ABSTRACT
The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatininduced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA expression (GSE66761) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the linear models for microarray data method and mRNA targets of DEMs were predicted using the miRWalk2.0 database. The crucial DEGs were screened by constructing a proteinprotein interaction (PPI) network and module analysis. Functions of target genes were analyzed using the database for annotation, visualization and integrated discovery. Small molecule drugs were predicted using the connectivity map database. As a result, 5 DEMs were identified to be shared and oppositely expressed in comparisons between AKI model and control groups, and between MSC treatment and AKI model groups. The 103 DEGs were overlapped with the target genes of 5 common DEMs, and the resulting list was used for constructing the miRNAmRNA regulatory network, including rnomiR210/Serpine1 and rnomiR378/Fos. Serpine1 (degree=17) and Fos (degree=42) were predicted to be hub genes according to the topological characteristic of degree in the PPI network. Function analysis indicated Serpine1 and Fos may be inflammationrelated. Furthermore, gliclazide was suggested to be a potential drug for the treatment of AKI because the enrichment score was the closest to 1 (0.9). In conclusion, it can be speculated that gliclazide may have a similar mechanism to MSC as a potential therapeutic agent for cisplatininduced AKI, by regulating miR210/Serpine1 and miR378/Fosmediated inflammation and cell apoptosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
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Oncogene Proteins v-fos
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Plasminogen Activator Inhibitor 1
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MicroRNAs
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Acute Kidney Injury
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Mesenchymal Stem Cells
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2019
Document type:
Article