Mechanisms controlling the switch between the pro- and anti-fibrotic functions of the long non-coding natural anti-sense to hyaluronan synthase 2

20% of the UK population has renal fibrosis and no interventions prevent/reverse its relentless fatal pathology.

This project uses state of the art molecular, biochemical and imaging techniques to investigate mechanisms underlying a newly-discovered long non-coding RNAswitch that controls whether cells take on a fibrotic or non-fibrotic phenotype.

Chronic-Kidney-Disease-(CKD) is common and rising in prevalence with 2% of the NHS budget spent on Renal Replacement Therapy. Renal interstitial-fibrosis is a key determinant of CKD-progression, and increased synthesis of the glycosaminoglycan, Hyaluronan-(HA) in renal tissues correlates with fibrosis and renal outcomes. Factors that regulate HA synthesis therefore influence CKD progression and we were the first research group to describe a unique mechanism by which expression of the HA synthetic enzyme, HAS2, is causally linked with fibrosis in vivo, and is a critical mediator of pro-fibrotic cell-phenotype in vitro. We have also recently described post-transcriptional regulation of HAS2 mRNA by a natural long non-coding RNA antisense, HAS2-AS1 and identified it as a novel regulator of renal fibrosis. This project will dissect, at the molecular level, the mechanisms that regulate HAS2-AS1 expression/function leading to a HA-dependent pro-fibrotic cell-phenotype and which can be used as potential novel therapeutic targets.

For further details of this project, please see our website: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/project/mechanisms-controlling-the-switch-between-the-pro-and-anti-fibrotic-functions-of-the-long-non-coding-natural-anti-sense-to-hyaluronan-synthase-2