Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney.
Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a potentially life-threatening condition. Histologically, ATN corresponds to necrosis and detachment of renal tubular epithelial cells. However, the tubules possess a considerable regenerative capacity and may be restored. We have previously identified a scattered population of progenitor-like cells within the proximal tubules, sharing marker expression with the parietal epithelial cells of Bowman's capsule as well as with renal tubules regenerating after ATN. In the present analysis, we use transmission electron microscopy, immunoelectron microscopy and immunofluorescence of human kidney cortex to further explore these cells. We demonstrate that the cells are smaller and have drastically fewer mitochondria than the surrounding proximal tubule cells. They also display strong expression of several structural proteins such as vimentin, collagen-7A1 and the tight junction protein claudin-1. To functionally assess these cells, we also developed a novel human kidney explant model of ATN demonstrating that the cells are more resilient to injury than the surrounding proximal tubular cells. Taken together the results suggest a novel robust cell type with a contrasting biological role to that of the bulk of proximal tubular epithelium.
Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden.
Jennifer
J
Hansson
Department of Laboratory Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Kjell
K
Hultenby
Department of Pathology-Lund, Division of Clinical Electron Microscopy, Laboratory Medicine Skåne, SE-221 85 Lund, Sweden.
Catharina
C
Cramnert
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Fredrik
F
Pontén
Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden.
Hannes
H
Jansson
Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden.
David
D
Lindgren
Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden.
Håkan
H
Axelson
Department of Laboratory Medicine, Center for Molecular Pathology, Lund University, Skåne University Hospital, Malmö, Jan Waldenströms gata 59, SE-205 02 Malmö, Sweden. Electronic address: martin.johansson@med.lu.se.
Martin E
ME
Johansson
D050476:Bowman Capsule / Q000166:cytology; D062445:Claudin-1 / Q000096:biosynthesis; D024143:Collagen Type VII / Q000096:biosynthesis; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology; D007683:Kidney Tubular Necrosis, Acute / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000648:ultrastructure; D013234:Stem Cells / Q000378:metabolism*; D014746:Vimentin / Q000096:biosynthesis
D062445:Claudin-1; D024143:Collagen Type VII; D014746:Vimentin
Acute tubular necrosis; Mitochondria; Progenitor cells; Proximal tubules; Tubular regeneration