Jan M. Williams, PhD
Professor and Graduate Program Director
Office: Research Wing, G758
Lab: (601) 984-1626
- Renal physiology
- Diabetes and hypertension-induced nephropathy
Hypertension- and diabetes are the most common causes of chronic kidney failure and end-stage renal disease (ESRD). The direct cost for Medicare treatment of the 400,000+ patients with ESRD exceeds $35 billion per year not including the cost to treat another 20 million people who exhibit progressive decline in kidney function. The prevalence of ESRD in African Americans with hypertension or diabetes is 4 times higher than in Caucasians. Despite the magnitude of these problems, little is known about the initiating factors underlying the pathogenesis of diabetes-induced nephropathy due to the lack of appropriate animal models that mimic the progression of the human disease.
Over the last few years, my laboratory has characterized several diabetic rodent models of chronic kidney disease such as the streptozotocin (STZ, Type 1)-Dahl salt-sensitive (S) and Type 2 Diabetic Nephropathy (T2DN) rats. Dahl S and T2DN rats are genetic models of hypertensive renal disease that develop progressive proteinuria, focal segmental glomerulosclerosis (FSGS) and renal fibrosis which eventually progress to ESRD. Both model systems exhibit histological changes in the kidney that resemble the lesions seen in patients with hypertension and diabetes such as thickening of the glomerular and tubular basement membranes, glomerular hypertrophy and mesangial matrix expansion. Previous studies have demonstrated that the early stages of diabetes are associated with increases in glomerular capillary pressure (Pgc) and glomerular filtration rate (GFR) that initiates the development of proteinuria and renal injury. However, the mechanism by which early alteration changes in renal hemodynamics promote the development of diabetes-induced nephropathy remains unclear.
Our laboratory has found that the expression of matrix metalloproteases (MMPs) are increased during the progression of renal injury in STZ-treated Dahl S and T2DN rats, and treatment with inhibitors of MMPs prevents the development of proteinuria and renal disease. The main focus of my laboratory is to determine the role of MMPs during the progression of diabetes-induced renal injury. Regardless of the mechanism involved, our data indicate that MMP inhibitors hold the potential to prevent the progression of renal disease in the millions of patients suffering from chronic kidney disease.