Identification of key microRNAs, transcription factors and genes associated with congenital obstructive nephropathy in a mouse model of megabladder.

OBJECTIVE: The present study aimed to investigate the molecular mechanism underlying congenital obstructive nephropathy (CON).

METHODS: The microarray dataset GSE70879 was downloaded from the Gene Expression Omnibus, including 3 kidney samples of megabladder mice and 4 control kidneys. Using this dataset, differentially expressed miRNAs (DEMs) were identified between the kidney samples from megabladder mice and controls, followed by identification of the target genes for these DEMs and construction of a DEM and target gene interaction network. Additionally, the target genes were subjected to Gene Ontology and pathway enrichment analyses, and were used for construction of a protein-protein interaction (PPI) network. Finally, regulatory networks were constructed to analyze transcription factors for the key miRNAs.

RESULTS: From 17 DEMs identified between kidney samples of megabladder mice and controls, 3 key miRNAs were screened, including mmu-miR-150-5p, mmu-miR-374b-5p and mmu-miR-126a-5p. The regulatory networks identified vascular endothelial growth factor A (Vegfa) as the common target gene of mmu-miR-150-5p and five transcription factors, including nuclear receptor subfamily 4, group A, member 2 (Nr4a2), Jun dimerisation protein 2 (Jdp2), Kruppel-like factor 6 (Klf6), Neurexophilin-3 (Nxph3) and RNA binding motif protein 17 (Rbm17). The gene encoding phosphatase and tensin homolog (Pten) was found to be co-regulated by mmu-miR-374b-5p and high mobility group protein A1 (Hmga1), whereas the kirsten rat sarcoma viral oncogene (Kras) was identified as a common target gene of mmu-miR-126a-5p and paired box 6 (Pax6).

CONCLUSIONS: In summary, the above-listed key miRNAs, transcription factors and key genes may be involved in the development of CON.