title: Nestin is a novel marker for renal tubulointerstitial injury in immunoglobulin A nephropathy.
abstract: 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.
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Tomioka
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: 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
chemical_list: D000199:Actins; D018952:Antigens, CD34; D015415:Biomarkers; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D003404:Creatinine