5 Increased dynamin expression precedes proteinuria in glomerular disease 95 Figure 3. Glomerular dynamin protein levels are increased in human proteinuric kidneys (A – H) Representative images of glomeruli immunostained for dynamin (A – D) or for cathepsin L (E – H) in a healthy control subject (A and E), a patient with diabetic nephropathy (B and F), a patient with lupus nephritis (C and G), and a patient with minimal change disease (D and H). (I and J) Summary of the percent glomerular positive area for dynamin (I) and cathepsin L (J) in patients with the indicated proteinuric kidney diseases. Dynamin protein expression is significantly higher in LN and MCD compared to control; *p < 0.05 versus control. Cathepsin L protein expression is significantly higher in LN, MCD and IgAN compared to control; *p < 0.05 versus control. (K) Summary of proteinuria data of the different patient groups. No correlation was found between the level of proteinuria and dynamin staining. Patients with MCD, FSGS and IgAN all had significantly more proteinuria than control patients; **p < 0.01, ***p < 0.001, MCD, minimal change disease; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; LN, lupus nephritis; DN, diabetic nephropathy. All images were taken at the same magnification; scale bar = 50 µm. Discussion Here, we investigated dynamin expression under proteinuric conditions in both patients and rats. In addition, we examined whether dynamin is involved in glomerular proteinuria, tubular proteinuria, or both. We found a significant increase in glomerular levels of Dnm2 and Dnm1 mRNA in Dahl rats prior to the onset of albuminuria. Also, we show that knocking down dynamin translation results in proteinuria in a zebrafish embryo model. Lastly, we found that glomerular levels of dynamin and cathepsin L protein are significantly increased in patients with proteinuric kidney disease.
RkJQdWJsaXNoZXIy MTk4NDMw