Dr SANELA REDZEPAGIC1, A/Prof. SARAH GLASTRAS1,2, A/Prof. MUH GEOT WONG3,4, Prof. DEBORAH BLACK3
1Renal Research Group, Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney,, Australia, 2Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney,, Australia, 3Faculty of Medicine and Health, The University of Sydney, Sydney,, Australia, 4Concord Repatriation General Hospital, Concord,, Australia
Aim
Delineate the mechanistic role of lncRNAs in preclinical models of DKD through systematic review.
Background
Exploring the role of long non-coding RNAs (>200nt long), one of the least investigated novel epigenetic mechanisms, in gene-expression regulation of DKD may lead to insights into DKD-pathogenesis and establish potential treatment-targets.
Methods
Electronic search from five bibliography-databases (Ovid-Medline, Embase, PubMed, Scopus, Web of Science) was conducted and studies included based on a protocol-specified criteria of any published original-experimental-controlled studies in English using in-vivo murine and/or in-vitro murine or human cell-models of DKD that explored lncRNAs-mechanisms. Studies were excluded if model is non-DKD, gene-modulation intervention or lncRNA mechanism were not reported. Two independent investigators conducted the search/screening, key study-characteristics were extracted, and study-quality assessed by SYRCLE’s risk-of-bias-tool (in-vivo), or NTP-OHAT recommendations for in-vitro studies.
Results
This search yielded 2002 articles with 144 qualitative studies extracted involving 77 different individual lncRNAs in preclinical DKD-models. Majority of studies explored the role of lncRNAs in pathogenesis of DKD. The five most common mechanisms were fibrosis, cell-viability/proliferation, cell-apoptosis, inflammation, oxidative stress. Most commonly investigated lncRNAs were MALAT1, TUG1, NEAT1, PVT1, ANRIL, GAS5, CASC2, MEG3, H19, KCNQ1OT1, MIAT, ZEB-AS1, of which lncRNA TUG1, GAS5, CASC2, ZEB-AS1, MEG3 had potentially protective role. The role of competing endogenous RNA (ceRNA) was often explored.
Conclusion
LncRNAs are implicated in a wide variety of pathogenic processes in DKD, with individual lncRNAs playing either a detrimental or protective role in fibrosis, inflammation, apoptosis & other molecular processes. Gene-modulation-interventions can limit burden of DKD. This review highlighted need for more standardised reporting of methodology in preclinical studies. The role of lncRNAs in DKD is an emerging field, requiring more research to fully establish their role.
Biography:
Dr Sanela Redzepagic MBBS BSc (Med) (UNSW), FRACP Nephrology.
Consultant Nephrologist & PhD-candidate (Renal Lab, Kolling Institute, University of Sydney with Prof. Pollock’s renal research-group, under current supervision by Prof. V. Cogger). Awarded the APA (RTP) scholarship & Ramsay Health Care Foundation stipend. Completed Basic Physician & Nephrology training at RPAH & East Coast Renal Network.
Sanela’s PhD-study:
- Investigating a role of a novel mechanism of long non-coding RNAs (lncRNAs) in DKD
- Investigating a novel antisense lncRNA Gm10603 & its relationship to its flanking protein-coding genes, particularly C2CD3, a primary cilia-gene, using gene-“knockdown” therapy to study downstream effects.