Down-Regulation of Human Long Non-Coding RNA LINC01187 Is Associated with Nephropathies

Background: Chronic kidney diseases affect a substantial percentage of the adult population worldwide, emphasizing the need for novel insights into the molecular mechanisms that control the onset and progression of renal diseases. Recent advances in genomics have uncovered a previously unanticipated link between the non-coding genome and human kidney diseases.  Methods: We screened and analyzed long non-coding RNAs (lncRNAs), previously identified in mouse kidneys by genome-wide transcriptomic analysis, for conservation in humans and differential expression in renal tissue from healthy and diseased individuals. Murine models of renal diseases were used to analyze selected lncRNAs expression. Moreover, the role of LINC01187 lncRNA was assed in human kidney cell line in vitro. Findings: Our data, suggest that LINC01187 is strongly down-regulated in human kidney tissues of patients with diabetic nephropathy and rapidly progressive glomerulonephritis, as well as murine models of  unilateral ureteral obstruction, anti-glomerular basement membrane and ischemia-reperfusion. LINC01187 overexpression in human kidney cells in vitro inhibits cell death indicating an anti-apoptotic function.  Interpretation: Collectively, these data suggest a negative association of LINC01187 expression with renal diseases implying a potential protective role. The new findings provide novel insights on the involvement of non coding genome in nephropathies. Funding Statement: This work was supported by: the European Research Council (agreement no. 742390) to Dimitrios Boumpas; the German Research Foundation (DFG; SFB/TRR57, SFB/TRR219, BO3755/3-1, BO3755/9-1, BO3755/13-1) and the German Federal Ministries of Education and Research (BMBF: STOP-FSGS-01GM1901A) to Peter Boor; Fondation Sante grant and the Hellenic Foundation for Research and Innovation (H.F.R.I) under the “First Call for H.F.R.I Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: 1782) to Panagiotis Politis. The ERCB-KFB was supported by the Else Kroner-Fresenius Foundation. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Samples were collected after signed consent forms were provided, following standard procedures from the Research Ethics Committee of each Institution. All procedures regarding animal experimentation were in accordance with the European Union Guidelines for the Care and Use of Laboratory Animals and approved by the local ethics committee of the National Institute for Health and Medical Research (INSERM) (for the Glomerulonephritis and Ischemia/Reperfusion models) and of the Biomedical Research Foundation of the Academy of Athens (BRFAA) (for the UUO model).