Submitted on May 11, 2006
Accepted on January 22, 2007
Expression of nestin in the podocytes of normal and diseased human kidneys
Wei Su1, Jing Chen1, Haichun Yang1, Li You1, Lan Xu1, Xiang Wang2, Ruixi Li3, Lu Gao3, Yong Gu1, Shanyan Lin1, Hong Xu4, Matthew D. Breyer5, and Chuan-Ming Hao6*
1 Nephrology, Huashan Hospital Fudan University, Shanghai, China
2 Urology, Huashan Hospital Fudan University, Shanghai, China
3 Anatomy and Embrology, Shanghai Medical School, Fudan University, Shanghai, China
4 Children Hospital Fudan University, Shanghai, China
5 Nephrology, Vanderbilt University Medical School, Nashville, Tennessee, United States
6 Nephrology, Vanderbilt University Medical School, Nashville, Tennessee, United States; Nephrology, Huashan Hospital Fudan University, Shanghai, China
* To whom correspondence should be addressed. E-mail: chuanming.hao{at}vanderbilt.edu.
The complex cyto-architecture of the podocyte is critical for glomerular permselectivity. The present study characterizes the expression of nestin, an intermediate filament protein, in human kidneys. In normal kidneys, nestin was detected at the periphery of glomerular capillary loops. Co-labeling showed nestin was expressed in WT1 positive cells. Within the podocyte, nestin immunoreactivity was present in the cell body and primary process. This was supported by immunoelectron microscopy (immuno-EM). Nestin also co-localized with vimentin in the periphery of capillary loops, but not in the mesangium. Nestin was not detected in other structures of the adult human kidney. To determine the potential role of nestin in proteinuria, nestin was examined in kidney biopsies from patients with or without proteinuria. These patients were diagnosed with IgA nephropathy (IgAN) with mild mesangial expansion but without proteinuria, IgA nephropathy with proteinuria, membranous nephropathy (MN) and focal segmental glomerular sclerosis (FSGS). The distribution of nestin in these biopsies was similar to that in the normal kidney. Semi-quantitative analysis of immunostaining showed that glomerular nestin expression in IgA nephropathy without proteinuira was not different from normal kidney, however nestin expression in kidneys of patients with IgA nephropathy and proteinuria, or MN and FSGS with proteinuria was significantly reduced compared to normal kidney (p<0.01). Reduced nestin mRNA expression in the patients with IgA nephropathy with proteinuria and FSGN was also observed by quantitative real time PCR. These studies suggest that nestin may play an important role in maintaining normal podocyte function in the human kidney.
