Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy.
OBJECTIVE
Nestin, an intermediate filament originally identified as a marker of neural progenitor cells, is transiently expressed in endothelial cells and tubuloepithelial cells during kidney development. However, in adult kidneys, podocytes are the only cells that express nestin. In this study, we examined tubulointerstitial nestin expression in human glomerulonephritis.


METHODS
Renal biopsy specimens obtained from 41 adult patients with immunoglobulin (Ig)A nephropathy were studied. Nestin expression was determined by immunohistochemical staining and estimated by digital image analysis. To identify the phenotype of nestin-positive cells, a double immunofluorescent study was performed for nestin and CD34 (a marker for endothelial cells) or alpha-smooth muscle actin (alpha-SMA, a marker for myofibroblasts).


RESULTS
In normal kidney, nestin expression was restricted to the podocytes and was not detected in tubular cells and tubulointerstitial cells. In contrast, increased nestin expression was observed at tubulointerstitial areas of IgA nephropathy. The degree of tubulointerstitial nestin expression was positively correlated with tubulointerstitial fibrosis (r = 0.546, P < 0.001). The double immunofluorescent study showed that most nestin-positive cells in the interstitium were co-stained with CD34 or alpha-SMA, suggesting that peritubular endothelial cells and tubulointerstitial myofibroblasts express nestin during the progression of tubulointerstitial injury. In addition, strong nestin expression was associated with deterioration of renal function.


CONCLUSIONS
Nestin expression is associated with tubulointerstitial injury and predicts renal prognosis in IgA nephropathy. Nestin could be a new marker for peritubular endothelial cell injury and tubulointerstitial fibrosis.
Tomioka
Mai
M
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Hiromura
Keiju
K
Sakairi
Toru
T
Takeuchi
Shigeru
S
Maeshima
Akito
A
Kaneko
Yoriaki
Y
Kuroiwa
Takashi
T
Takeuchi
Toshiyuki
T
Nojima
Yoshihisa
Y
D000199:Actins / Q000032:analysis; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis*; D007564:Japan; D053208:Kaplan-Meier Estimate; D007684:Kidney Tubules / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D064231:Nestin; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000378:metabolism; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors
D000199:Actins; D018952:Antigens, CD34; D015415:Biomarkers; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D003404:Creatinine