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Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
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2014 (English)In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 45, no 2, 382-393 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2014. Vol. 45, no 2, 382-393 p.
Keyword [en]
Progenitor cells, Acute tubular necrosis, Tubular regeneration, Mitochondria, Proximal tubules
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-219961DOI: 10.1016/j.humpath.2013.10.003ISI: 000330551300024OAI: oai:DiVA.org:uu-219961DiVA: diva2:704588
Available from: 2014-03-12 Created: 2014-03-09 Last updated: 2017-12-05Bibliographically approved

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Pontén, Fredrik

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