Identification of crucial miRNAs and the targets in renal cortex of hypertensive patients by expression profiles.
BACKGROUND
Defect in kidney is one major reason of hypertension. The study aimed ao uncovering the regulatory mechanisms of miRNAs and the targets in hypertensive kidney.


METHODS
Gene expression profile of GSE28345 and miRNA expression profile of GSE28283 were downloaded from GEO database. After data preprocessing, differently expressed genes (DEGs) and miRNAs (DE-miRs) were identified using limma package. Then targets of miRNAs were predicted according to information in relevant databases. Function and pathway enrichment analyses were performed for DEGs using DAVID software. Furthermore, protein-protein interaction (PPI) networks were constructed for up- and down-regulated genes, respectively, using the Cytoscape. Additionally, for down-regulated DEGs, the integrated regulatory network was established combining PPI network with the miRNA-mRNA interactions.


RESULTS
As a result, 285 DEGs were identified, including 177 up-regulated and 108 down-regulated genes. Combined with the predicted targets of miRNAs, 22 up-regulated DE-miRs were identified. In the integrated network for down-regulated DEGs, three crucial nodes were identified as ASPN, COL12A1, and SCN2A. ASPN was predicted as target of miR-21 and miR-374b, and COL12A1 was the target of miR-30e, miR-21, and miR-195, while SCN2A was the target of miR-30e, miR-374b, and miR-195. Notably, COL12A1 and ASPN were linked with each other in the network.


CONCLUSIONS
Three crucial genes were identified in hypertensive kidney, such as COL12A1, ASPN, and SCN2A. ASPN might co-function with COL12A1, and they both might be the targets of miR-21. SCN2A might be a novel target of miR-30e and miR-374b. However, more experiments are needed to validate these results.
a Department of Pediatrics , The First Hospital of Jilin University , Changchun , China.
Guohua
G
Wang
a Department of Pediatrics , The First Hospital of Jilin University , Changchun , China.
Lan
L
Wu
b Department of Nephrology , The First Hospital of Jilin University , Changchun , China.
Zhi
Z
Chen
a Department of Pediatrics , The First Hospital of Jilin University , Changchun , China.
Jinghui
J
Sun
D024082:Collagen Type XII / Q000235:genetics*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D015854:Up-Regulation
C439889:ASPN protein, human; C547160:COL12A1 protein, human; D024082:Collagen Type XII; D016326:Extracellular Matrix Proteins; C524940:MIRN21 microRNA, human; C546086:MIRN30b microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human
Hypertension; kidney; miRNA; microarray; protein–protein interaction