Intrinsic epithelial cells repair the kidney after injury.
Understanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%-95% of tubular epithelial cells, but no interstitial cells, were labeled with either beta-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney.
Humphreys
Benjamin D
BD
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Room 550, 4 Blackfan Circle, Boston, MA 02115, USA. bhumphreys@partners.org
Valerius
M Todd
MT
Kobayashi
Akio
A
Mugford
Joshua W
JW
Soeung
Savuth
S
Duffield
Jeremy S
JS
McMahon
Andrew P
AP
Bonventre
Joseph V
JV
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D012038:Regeneration; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors