title: Proliferative capacity of stem/progenitor-like cells in the kidney may associate with the outcome of patients with acute tubular necrosis.
abstract: Animal studies indicate that adult renal stem/progenitor cells can undergo rapid proliferation in response to renal injury, but whether the same is true in humans is largely unknown. To examine the profile of renal stem/progenitor cells responsible for acute tubular necrosis in human kidney, double and triple immunostaining was performed using proliferative marker and stem/progenitor protein markers on sections from 10 kidneys with acute tubular necrosis and 4 normal adult kidneys. The immunopositive cells were recorded using 2-photon confocal laser scanning microscopy. We found that dividing cells were present in the tubules of the cortex and medulla, as well as the glomerulus in normal human kidney. Proliferative cells in the parietal layer of Bowman capsule expressed CD133, and dividing cells in the tubules expressed immature cell protein markers paired box gene 2, vimentin, and nestin. After acute tubular necrosis, Ki67-positive cells in the cortex tubules significantly increased compared with normal adult kidney. These Ki67-positive cells expressed CD133 and paired box gene 2, but not the cell death marker, activated caspase-3. In addition, the number of dividing cells increased significantly in patients with acute tubular necrosis who subsequently recovered, compared with patients with acute tubular necrosis who consequently developed protracted acute tubular necrosis or died. Our data suggest that renal stem/progenitor cells may reside not only in the parietal layer of Bowman capsule but also in the cortex and medulla in normal human kidney, and the proliferative capacity of renal stem/progenitor cells after acute tubular necrosis may be an important determinant of a patient's outcome.
authors.affiliation: Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang 310016, China. youxinye3@yahoo.com
authors.forename: Youxin
authors.initials: Y
authors.lastname: Ye
authors.forename: Bingyin
authors.initials: B
authors.lastname: Wang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Jiang
authors.forename: Weiming
authors.initials: W
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Jin
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Ying
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoou
authors.initials: X
authors.lastname: Mao
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D050476:Bowman Capsule / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002455:Cell Division; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D051762:PAX2 Transcription Factor / Q000378:metabolism; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D014746:Vimentin