NDT Advance Access published online on March 20, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn100
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Dendrin expression in glomerulogenesis and in human minimal change nephrotic syndrome
1 Departments of Clinical Science, Intervention and Technology (CLINTEC, Division of Renal Medicine) 2 Medical Biochemistry and Biophysics 3 Laboratory Medicine (Division of Pathology), Karolinska Institutet, Stockholm, Sweden
Correspondence and offprint requests to: Fredrik Dunér, Department of Renal Medicine, K56, Karolinska University Hospital, Huddinge, 141-86 Stockholm, Sweden. Tel: +46-8-58580000; Fax: +46-8-711-47-42; E-mail: fredrik.duner{at}ki.se
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Abstract |
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Background. Dendrin is an 81-kD cytosolic protein hitherto described in the brain, where it is associated with the actin cytoskeleton. Recently, we found dendrin in foot processes of mouse glomerular podocytes. Here we describe its expression both during mouse glomerulogenesis and in the normal and diseased human kidney for the first time.
Methods. Dendrin expression was characterized using RT–PCR and immunohistochemistry and semi-quantified using immunoelectron microscopy.
Results. In glomerulogenesis, dendrin mRNA and protein appeared first at the early capillary loop stage. It was concentrated to the pre-podocytes on the basal side of podocalyxin, an apical cell membrane marker. In human tissue, dendrin transcripts were detected in the brain and kidney. In the mature kidney dendrin localized solely in the podocytes, close to the filtration slit diaphragms. A comparison with the slit-associated protein zonula occludens-1 (ZO-1) was done in minimal change nephrotic syndrome (MCNS). Dendrin and ZO-1 were re-distributed from slit regions to the podocyte cytoplasm in areas with foot process effacement (FPE). In areas without FPE, dendrin and ZO-1 distributions were unchanged compared to controls. The total amounts of dendrin or ZO-1 markers were unchanged. This differs from nephrin that, according to our previous results, is also decreased in non-effaced areas.
Conclusions. The expression of dendrin during glomerulogenesis and in the normal human kidney is similar to that previously shown for nephrin, which suggests that dendrin associates with the slit diaphragm complex. In MCNS patients, dendrin and ZO-1 are re-distributed within the podocytes. Whether this is a cause or a consequence of FPE remains unclear.
Keywords: dendrin; glomerulogenesis; immunoelectron microscopy; nephrotic syndrome
Received for publication: 12.12.07
Accepted in revised form: 1. 2.08