Dissecting the role of miR-214 in TGF-beta dependent and independent fibrotic renal pathology

People with chronic kidney disease have kidneys that are not functioning properly. The number of patients suffering with the disease is increasing. Sufferers can progress to kidney failure which eventually requires the patient to need dialysis and ultimately a kidney transplant. The cost of treating these patients is £1.45 billion/year, which places a burden on the NHS. There is a need to improve treatment options for these patients. This proposal will investigate important molecules called microRNAs that are involved in the initiation and/or progression of kidney disease. These molecules work by changing expression of defined protein in cells. This proposal aims to understand how a particular miRNA, miR-214 influences scarring of the kidney which is the common endpoint of all progressive kidney diseases. We have already shown that inhibiting miR-214 is beneficial in renal disease and blocks scar formation. However, it is not clear how miR-214 is acting. This project will dissect which pathways in the cell miR-214 is influencing and thus elucidate novel pathways which could be targeted therapeutically. The proposal will use a variety of in vitro and in vivo methodologies to understand the role of miR-214, as well as human samples to confirm importance in human disease.