title: Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases.
abstract: 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 TGFβ 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.
authors.affiliation: Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Arvaniti
authors.affiliation: HybridStat Predictive Analytics, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Moulos
authors.affiliation: Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Vakrakou
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chatziantoniou
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chadjichristos
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kavvadas
authors.affiliation: Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Charonis
authors.affiliation: Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Panagiotis K
authors.initials: PK
authors.lastname: Politis
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000503:physiopathology*; D020869:Gene Expression Profiling; D007674:Kidney Diseases / Q000503:physiopathology*; D051379:Mice; D014517:Ureteral Obstruction / Q000150:complications*