Nestin expression in the kidney with an obstructed ureter.
Nestin is an intermediate filament protein originally identified in neuroepithelial stem cells. This cytoskeletal-associated protein is also expressed in some non-neuronal organs including renal tubular cells and glomerular endothelial cells during kidney development. Little is known, however, about nestin expression in the kidney during injury. In this study, we find nestin expression induced in renal tubular and interstitial myofibroblasts in the adult rat kidney following unilateral ureteral obstruction. The degree of nestin expression was well correlated with the degree of tubulointerstitial fibrosis. Immunohistochemical identification of specific nephron segments showed that nestin was primarily expressed by proximal tubules, partially by distal tubules and thick ascending limbs of Henle but not by collecting ducts. The nestin-positive tubular cells also expressed vimentin and heat-shock protein 47 (HSP47) suggesting these cells reverted to a mesenchymal phenotype. Not all vimentin- or HSP-expressing cells expressed nestin; however, suggesting that nestin is distinct from these conventional mesenchymal markers. Nestin expression was also found associated with phenotypical changes in cultured renal cells induced by hypoxia or transforming growth factor-beta. Nestin expression was located in hypoxic regions of the kidney with an obstructed ureter. Our results indicate that nestin could be a novel marker for tubulointerstitial injury.
Sakairi
T
T
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Hiromura
K
K
Yamashita
S
S
Takeuchi
S
S
Tomioka
M
M
Ideura
H
H
Maeshima
A
A
Kaneko
Y
Y
Kuroiwa
T
T
Nangaku
M
M
Takeuchi
T
T
Nojima
Y
Y
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D064231:Nestin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000150:complications*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D050958:HSP47 Heat-Shock Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014746:Vimentin; C577486:Nes protein, rat; C494662:Serpinh1 protein, rat; C498862:Acta2 protein, rat