In:
European Journal of Clinical Investigation, Wiley, Vol. 46, No. 3 ( 2016-03), p. 213-226
Abstract:
Micro RNA s (mi RNA s) contribute to chronic kidney disease (CKD) progression via regulating mRNA s involved in renal homeostasis. However, their association with clinical outcome remains poorly understood. Materials and methods We performed mi RNA and mRNA expression profiling on renal biopsy sections by qPCR (mi RNA ) and microarrays ( mRNA ) in a discovery ( n = 43) and in a validation ( n = 29) cohort. mi RNA s differentiating stable and progressive cases were inversely correlated with putative target mRNA s, 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 mi RNA s correlated with upregulated 29 target mRNA s 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 mRNA s: Reduced expression of miR‐206 in progressive disease correlated with the upregulation of target mRNA s participating in inflammatory pathways ( CCL 19, CXCL 1, IFNAR 2, NCK 2, PTK 2B, PTPRC , RASGRP 1 and TNFRSF 25). Progressive cases also showed a lower expression of miR‐532‐3p and an increased expression of target transcripts involved in apoptosis pathways ( MAP 3K14, TNFRSF 10B/ TRAIL ‐R2, TRADD and TRAF 2). In the validation cohort, we confirmed the decreased expression of miR‐206 and miR‐532‐3p, and the inverse correlation of these mi RNA s with the expression of nine of the 12 target genes. The levels of the identified mi RNA s and the target mRNA s correlated with clinical parameters and histological damage indices. Conclusions These results suggest the involvement of specific mi RNA s and mRNA s in biological pathways associated with the progression of CKD.
Type of Medium:
Online Resource
ISSN:
0014-2972
,
1365-2362
DOI:
10.1111/eci.2016.46.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2004971-7
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