title: Proximal tubular cells contain a phenotypically distinct, scattered cell population involved in tubular regeneration.
abstract: Regeneration of injured tubular cells occurs after acute tubular necrosis primarily from intrinsic renal cells. This may occur from a pre-existing intratubular stem/progenitor cell population or from any surviving proximal tubular cell. In this study, we characterize a CD24-, CD133-, and vimentin-positive subpopulation of cells scattered throughout the proximal tubule in normal human kidney. Compared to adjacent 'normal' proximal tubular cells, these CD24-positive cells contained less cytoplasm, fewer mitochondria, and no brush border. In addition, 49 marker proteins are described that are expressed within the proximal tubules in a similar scattered pattern. For eight of these markers, we confirmed co-localization with CD24. In human biopsies of patients with acute tubular necrosis (ATN), the number of CD24-positive tubular cells was increased. In both normal human kidneys and the ATN biopsies, around 85% of proliferating cells were CD24-positive - indicating that this cell population participates in tubular regeneration. In healthy rat kidneys, the novel cell subpopulation was absent. However, upon unilateral ureteral obstruction (UUO), the novel cell population was detected in significant amounts in the injured kidney. In summary, in human renal biopsies, the CD24-positive cells represent tubular cells with a deviant phenotype, characterized by a distinct morphology and marker expression. After acute tubular injury, these cells become more numerous. In healthy rat kidneys, these cells are not detectable, whereas after UUO, they appeared de novo - arguing against the notion that these cells represent a pre-existing progenitor cell population. Our data indicate rather that these cells represent transiently dedifferentiated tubular cells involved in regeneration.
authors.affiliation: Division of Nephrology and Immunology, University Hospital of the Aachen University of Technology (RWTH), Aachen, Germany. bsmeets@ukaachen.de
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.forename: Henry
authors.initials: H
authors.lastname: Dijkman
authors.forename: Shagun V
authors.initials: SV
authors.lastname: Sharma
authors.forename: Peggy
authors.initials: P
authors.lastname: Jirak
authors.forename: Fieke
authors.initials: F
authors.lastname: Mooren
authors.forename: Katja
authors.initials: K
authors.lastname: Berger
authors.forename: Jörg
authors.initials: J
authors.lastname: Bornemann
authors.forename: Irwin H
authors.initials: IH
authors.lastname: Gelman
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Moeller
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D051927:CD24 Antigen / Q000378:metabolism; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000648:ultrastructure; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D014517:Ureteral Obstruction / Q000150:complications / Q000473:pathology; D014746:Vimentin / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D051927:CD24 Antigen; C497889:CD24 protein, human; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat; D014746:Vimentin