Mechanisms of Interstitial Fibrosis in Diabetic Nephropathy

Abstract

In studies regarding the progression of diabetic nephropathy (DN), tubular injury, such as tubular atrophy and tubulointerstitial fibrosis, has been long underestimated, and research has been focused mainly on glomerular pathology. Recently, more studies evaluated tubular damage, since it became obvious that tubulointerstitial fibrosis and tubular atrophy show a major correlation with the declined renal function in DN. Hyperglycemia induces tubular atrophy in DN through mechanisms that are identical to those thought to cause interstitial fibrogenesis. The biologic processes leading to kidney fibrosis are not simply just rigid mechanisms but rather a complex interaction between pathologic changes in renal cells and the pathobiologic activity of profibrotic factors. Multiple cell types and numerous pathways are activated in the kidney during the course of diabetes, and all individually or collectively play a role in the development and progression of interstitial fibrosis. A comprehensive understanding of the underlying mechanisms and downstream pathways involved in the tubulointerstitial fibrosis is mandatory to develop groundbreaking therapeutic options and novel clinical strategies in the treatment of DN.