Renal microRNA- and RNA-profiles in progressive chronic kidney disease

Background: MicroRNAs (miRNAs) contribute to chronic kidney disease (CKD) progression via regulating mRNAs involved in renal homeostasis. However, their association with clinical outcome remains poorly understood. Materials and methods: We performed miRNA and mRNA expression profiling on renal biopsy sections by qPCR (miRNA) and microarrays (mRNA) in a discovery (n=43) and in a validation (n=29) cohort. miRNAs differentiating stable and progressive cases were inversely correlated with putative target mRNAs, which were further characterized by pathway analysis using KEGG pathways. Results: miR-30d, miR-140-3p, miR-532-3p, miR-194, miR-190, miR-204 and miR-206 were downregulated in progressive cases. These seven miRNAs correlated with upregulated 29 target mRNAs involved in inflammatory response, cell-cell interaction, apoptosis and intra-cellular signalling. In particular, miR-206 and miR-532-3p were associated with distinct biological processes via the expression of their target mRNAs: Reduced expression of miR-206 in progressive disease correlated with the upregulation of target mRNAs participating in inflammatory pathways (CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1 and TNFRSF25). Progressive cases also showed a lower expression of miR-532-3p and an increased expression of target transcripts involved in apoptosis pathways (MAP3K14, TNFRSF10B/TRAIL-R2, TRADD and TRAF2). In the validation cohort, we confirmed the decreased expression of miR-206 and miR-532-3p, and the inverse correlation of these miRNAs with the expression of nine of the 12 target genes. The levels of the identified miRNAs and the target mRNAs correlated with clinical parameters and histological damage indices. Conclusions: These results suggest the involvement of specific miRNAs and mRNAs in biological pathways associated with the progression of CKD.

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