IMPC: Investigating the role of Olfml2b and Gpr176 in renal fibrosis using KO mice

Lead Research Organisation: University of Edinburgh
Department Name: Centre for Cardiovascular Science


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Technical Summary

Chronic kidney disease affects up to 5% of the UK population and is a major risk factor for heart disease and kidney failure, which may require dialysis or kidney transplantation. Scarring is observed in the kidney in all forms of kidney disease, regardless of the original diagnosis and more severe scarring predicts an increased likelihood of disease progression. Hence therapies that reduce the severity of renal scarring are being sought to treat patients with chronic kidney disease. A key aim of the research performed by our groups and the focus of the current project is to understand the molecular pathways that cause scarring in the kidney.
We have identified that the expression of 2 genes, olfactomedin-like 2b (Olfml2b) and G-protein coupled receptor 176 (Gpr176), is increased in the kidney in experimental models of renal scarring and in patients with chronic kidney disease. Furthermore, the expression of these genes is closely related to that of genes known to be involved in renal scarring, such as collagen. Hence, while the function of these genes is not yet certain, we hypothesise that they may be involved in the process of scarring in patients with kidney disease. The aim of the current research is to determine whether this is indeed the case.
To answer this question, we will employ mice in which either the Olfml2b or the Gpr176 genes have been removed by genetic manipulation. We will employ a number of pre-clinical models of kidney scarring. By comparing the amount of scarring in the kidney at post mortem between mice that have the Olfml2b gene removed and mice which have a normal Olfml2b gene, we can determine whether the gene is involved in kidney scarring. Similar studies will be conducted for mice with and without the Gpr176 gene.
Hence, we will be able to determine whether our hypothesis that these genes are implicated in renal scarring is correct. If this is indeed true, future studies will determine how these genes function during scarring and whether therapies could be developed to target these genes and prevent renal scarring and progression of kidney disease.


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Description Selective targeting of GPR176 as a paradigm for the development of novel renal anti-fibrotic drugs.
Amount £483,864 (GBP)
Funding ID SF_001_20181122 
Organisation Kidney Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2019 
End 11/2024