SEMA3C · Genetic dissection of the SEMA3C/Neuropilin 1 signalling pathway in Chronic Kidney Disease progression

Genetic dissection of the SEMA3C/Neuropilin 1 signalling pathway in Chronic Kidney Disease progression

Regardless of the initial insult, human Chronic Kidney Disease (CKD) is characterised by progressive destruction of the renal parenchyma and the loss of functional nephrons, the filtering units of a kidney. The worldwide incidence of CKD has reached epidemic proportions and is a major health care burden, with an estimated 10-14% of the adult population known to have CKD. Diabetes and hypertension are major contributors to the global burden of the disease and are important CKD risk factors. Inexorable progression to kidney failure is predicted for many CKD patients with high risk of becoming dependent on renal replacement therapies (hemodialysis or transplantation). The financial impact of CKD is large, with particularly high costs relating to renal replacement therapies. For instance, the annual cost of CKD to the French Securite Sociale is estimated at €3.5 billion. The only option for reducing the dialysis population or for keeping it stable over the long term is to improve the early detection of CKDs. The diagnosis currently depends on rather late markers of kidney injury such as albuminuria or on decreased kidney functions (i.e. abnormal glomerular filtration rate). A key challenge for medical planning is to better understand the mechanisms of CKD progression in order to target pharmaceutical interventions at the early stages of the disease. This area of research is receiving increasing attention as the discovery of novel therapeutic targets/predictive biomarkers of renal fibrosis will facilitate the development of preventive therapies. Our research has established a novel pathway as a valid drug target in this area. The rationale for this contention is based on our data implicating the protein SEMA3C and its receptor NRP1 as having a fundamental role in CKD progression. Our project investigated the disease biology of CKD and provided an improved mechanistic understanding of the disease. Our work established a hierarchy towards using the semaphorin-neuropilin signalling pathway as novel therapeutic targets in kidney disease and opened up new directions for the development of novel treatments targeting this disease spectrum. Furthermore, our project has the potential to provide a new biomarker that will be used to set up rapid, reliable and non-invasive tests for monitoring and prediction of CKD.

Data: CORDIS, © European Union