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Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new
molecular players in kidney diseases
#MMPMID27189340
Arvaniti E
; Moulos P
; Vakrakou A
; Chatziantoniou C
; Chadjichristos C
; Kavvadas P
; Charonis A
; Politis PK
Sci Rep
2016[May]; 6
(?): 26235
PMID27189340
show ga
Transcriptome analysis by RNA-seq technology allows novel insights into gene
expression and regulatory networks in health and disease. To better understand
the molecular basis of renal fibrosis, we performed RNA-seq analysis in the
Unilateral Ureteric Obstruction (UUO) mouse model. We analysed sham operated, 2-
and 8-day post-ligation renal tissues. Thousands of genes with statistical
significant changes in their expression were identified and classified into
cellular processes and molecular pathways. Many novel protein-coding genes were
identified, including critical transcription factors with important regulatory
roles in other tissues and diseases. Emphasis was placed on long non-coding RNAs
(lncRNAs), a class of molecular regulators of multiple and diverse cellular
functions. Selected lncRNA genes were further studied and their transcriptional
activity was confirmed. For three of them, their transcripts were also examined
in other mouse models of nephropathies and their up- or down-regulation was found
similar to the UUO model. In vitro experiments confirmed that one selected lncRNA
is independent of TGF? or IL1b stimulation but can influence the expression of
fibrosis-related proteins and the cellular phenotype. These data provide new
information about the involvement of protein-coding and lncRNA genes in
nephropathies, which can become novel diagnostic and therapeutic targets in the
near future.
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