Effects Of Shear Stress On The Expression Of Megalin/cubilin And Mechanism Of Renal Tubulointerstitial Damage In The Early Stage Of Diabetic Nephropathy

Background: Diabetic nephropathy(DN) is an important chronic diabetic complication. It is the most prevalent cause of chronic renal failure and end-stage renal disease in the Western world and can account for 40% of the patient requiring renal replacement therapy. Although mesangial expansion, glomerular hypertrophy and thickening of the glomerular basement membrane leading to hyperfiltration and micalbuminuria are hallmarks of DN, the tubulointerstitium of the diabetic kidney has become a major focus of study with considerable advances having been made in the understanding of its role in the pathogenesis of DN over the last decade. In renal proximal tubules, as in blood vessels, shear stress may happen. Moreover, the flow in the initial portion of the proximal tubule corresponds to the single nephron glomerular filtration rate(GFR). It is postulated that the increase in GFR in the early stage of DN results initially in a similar increase in the linear velocity of tubular structure and reabsorptive function of the proximal tubule. The renal expression of megalin and cubilin, the two large membrane-...