Kidney transcriptome analysis of rats (Rattus norvegicus) revealed induction of renal injury and damage markers in response to melamine

Abstract

Objectives: Melamine is a major environmental indigestible pollutant molecule that represents a pertinent risk to human health on a daily bases. The focus of the current study was the investigation of melamine effects on the rat (Ratus norvegicus) kidney transcriptome for detecting changes in gene expression during the early stages of the kidney damage. Methods: Melamine was administered for 1 month to rats at 60 and 120 mg/kg/day to investigate its impact on the whole transcriptome of rat kidney. Transcriptome developed from mRNA of kidney cells was established using Illumina NovaSeq 6000 System with paired end sequencing of 100 bp with sequencing depth of 60 million reads and sequencing coverage of 6 Gb. Results: Results indicated the upregulation of 379 and 718 genes in the M60 and the M120 groups consecutively and the downregualtion of 167 and 392 in the M60 and the M120 groups consecutively. Also, melamine administration significantly enriched 2329 GO (Gene Ontology) terms (1890 BP terms, CC 191 terms, 248 MF terms) and 198 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Differentially expressed genes (DEGs) were related to process involved in kidney functions as well as early stages of kidney injury and fibrosis. These included cell–cell adhesion, cell-matrix adhesion, cytoskeleton organization, response to stress, olfactory transduction and perception, and several interesting kidney function markers. The enriched GO terms and KEGG pathways were also related to the DEGs groups. Conclusions: Results of the current study confirm that subchronic sublethal levels of melamine were able to initiate the early stages of kidney injury and fibrosis and introduce some early markers of kidney injury in the early diagnosis of kidney damage.

Keywords

• Melamine
• Rat
• Kidney
• Transcriptome
• Differentially expressed genes
• Kidney function markers