Identifying Key MicroRNAs Targeted by Narenmandula in a Rodent Nephropathy Model

Abstract

Background. Untreated nephropathy can progress to renal failure. The traditional Mongolian remedy Narenmandula regulates the kidney “yang.” This study aimed to identify key microRNAs (miRNAs) targeted by Narenmandula in a rat model of nephropathy. Methods. Fifteen rats exhibiting normal renal function were randomized to three study arms. Nephropathy was induced in n = 10 rats using doxorubicin hydrochloride, followed by either Narenmandula treatment (treatment group) or no treatment (control group). In n = 5 rats, no doxorubicin was given and renal function remained unchanged (healthy group). Microarray analysis identified miRNAs which were differentially expressed (DE-miRNAs) between groups. Target genes of DE-miRNAs were predicted using miRWalk version 2.0, followed by enrichment analysis using DAVID, and construction of the miRNA coregulatory network using Cytoscape. Results. Nephropathy was successfully induced, with doxorubicin resulting in differential expression of 3645 miRNAs (1324 upregulated and 2321 downregulated). Narenmandula treatment induced differential expression of a total of 159 miRNAs (102 upregulated and 57 downregulated). Upregulated DE-miRNAs (e.g., miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, and miR-30e-5p) and downregulated DE-miRNAs (e.g., miR-330-3p and miR-214-3p) regulated a high number of target genes. Moreover, the miRNA pairs (e.g., miR-195-5p—miR-497-5p, miR-181a-5p—miR-181c-5p, and miR-30e-5p—miR-30a-5p) coregulated a high number of genes. Enrichment analysis indicated functional synergy between miR-30e-5p—miR-30a-3p, miR-34a-5p—miR-30e-5p, miR-30e-5p—miR-195-3p, and miR-30a-3p—miR-195-3p pairs. Conclusion. Narenmandula may modulate doxorubicin-induced nephropathy via targeting miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, miR-30e-5p, miR-330-3p, miR-214-3p, miR-34a-5p, miR-30a-3p, and miR-30a-5p.