Thursday 9th March - World Kidney Day
Most forms of Chronic Kidney Disease (CKD) result in renal fibrosis. Renal fibrosis is when the kidney tissue becomes scarred, which results in deterioration of kidney function. In England alone, there were over 1.7 million people registered with CKD in 2008/9, costing the NHS £1.45 billion.
CKD is a multifactorial disease with various risk factors including diabetes, hypertension and smoking.
The current treatments available are very limited, with dialysis and transplantation being the only options for end-stage renal disease.
The incidence of CKD is increasing due to an ageing population and increasing incidence of diabetes, therefore, the discovery of new therapeutic targets for CKD is vital.
A protein called SMAD3 is known to have an important role in the development of renal fibrosis. When SMAD3 levels are reduced, fibrosis is significantly reduced. Unfortunately, no SMAD3 inhibitors have been developed to be used clinically. Therefore, other factors that affect SMAD3 activity must be identified.
We have identified a novel interaction between SMAD3 and another protein called SET9. When we reduce the levels of SET9 in kidney cells, we see a reduction in the markers of fibrosis which include Collagen I and aSMA.
Other markers of fibrosis include abnormal migration and contraction of kidney cells. When we apply the SET9 inhibitor to kidney cells, this abnormal migration and contraction of the cells is significantly reduced.
In conclusion, SET9 provides a promising target in renal fibrosis and the use of SET9 inhibitors could prove as a useful treatment for CKD.
Human Kidney Cells
Collagen l - no treatment Collagen l - SET9 inhibitor treatment
aSMA - no treatment aSMA - SET9 inhibiotr treatment
Human kidney cells were treated with or without SET9 inhibitor and then stained for fibrotic markers Collagen I or aSMA. Cells treated with the SET9 inhibitor show a reduction in Collagen I and aSMA, indicating a reduction in renal fibrosis compared to non-treated cells.