Investigation into the role of human long non-coding RNA 01187 in renal diseases

Postgraduate Thesis uoadl:2777391 351 Read counter

Unit:
Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and Bioinnovation
Library of the School of Health Sciences
Deposit date:
2018-07-06
Year:
2018
Author:
Manolakou Theodora
Supervisors info:
Παναγιώτης Πολίτης, Ερευνητής Γ, Ίδρυμα Ιατροβιολογικών Ερευνών, Ακαδημία Αθηνών (ΙΙΒΕΑΑ)
Αριστείδης Χαρώνης, Ερευνητής Α, Ίδρυμα Ιατροβιολογικών Ερευνών, Ακαδημία Αθηνών (ΙΙΒΕΑΑ)
Δημήτριος Μπούμπας, Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Investigation into the role of human long non-coding RNA 01187 in renal diseases
Languages:
English
Translated title:
Investigation into the role of human long non-coding RNA 01187 in renal diseases
Summary:
New sequencing technologies have offered novel insights into the organization, activity and regulation of the human genome. The largest amount of the genome is transcribed producing substantial numbers of formerly unidentified regulatory RNA species with critical involvement in human diseases. To this end, we have previously identified a large number of differentially expressed long non coding RNAs (lncRNAs) in the murine model of Unilateral Ureteric Obstruction (UUO). Here, we focused on one of these lncRNAs, human long intergenic noncoding RNA 01187 (LINC01187) and its mouse homolog (Gm12121long) in human and rodent kidney disorders. In particular, we show that the murine homolog, Gm12121long, is strongly down-regulated after ligation in the UUO mouse model. Moreover, chromatin immunoprecipitation assays revealed a concomitant reduction in the recruitment of RNA polymerase II and histone 3 tri-methylation in Lysine 4 (H3K4me3) on the promoter region of Gm12121long in this model, indicating direct repression at the chromatin/transcription level. Similar reduction in expression was also observed in two other murine models, the nephrotoxic serum-induced glomerulonephritis (NTS-induced GN) and the Ischemia/reperfusion (I/R). These results, along with the high conservation of the promoter sequence among species and the fact that the expression of both murine and human homologs are reported to be highly renal specific (data from ENCODE and GTEx databases), prompted us to examine the role of human homolog in renal pathologies. Thus, detailed investigation of LINC01187 expression levels in human samples from different sources and pathological situations shows a significant reduction of its expression in diseased versus healthy kidneys. In addition, interrogation of its gene expression in microdissected renal biopsies of the European Renal cDNA Bank (ERCB) confirmed major reduction in expression in the cases of rapidly progressive glomerulonephritis (RPGN) and diabetic nephropathy (DN), both in the glomerular and the tubular compartment. Furthermore, by in situ hybridization studies using healthy and pathological renal tissues (DN, RPGN and Lupus Nephritis), we observed strong expression of LINC01187 in elongated peri-glomerular cells, peri-tubular, certain glomerular cells as well as in cells around arteries in the healthy tissue and the case of LN, whereas there was almost complete lack of signal in the cases of DN and RPGN. In conclusion, our data suggest a critical role of a newly identified lncRNA, LINC01187, in renal diseases. The results from this study will broaden our knowledge on the involvement of lncRNAs in nephropathies and will help design more specific, targeted therapeutics in the near future.
Main subject category:
Health Sciences
Keywords:
Renal diseases, Molecular biology, Transcriptome, Long non-coding RNAs, Animal models, In situ hybridization
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
67
Number of pages:
59
File:
File access is restricted only to the intranet of UoA.

DissertationMSc_MANOLAKOU.pdf
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File access is restricted only to the intranet of UoA.