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J Pathol. 2015 Jun;236(2):251-63. doi: 10.1002/path.4514. Epub 2015 Mar 4.

Exploring the origin and limitations of kidney regeneration.

Author information

1
Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
3
Development II, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan.
4
TMK Project, Kyoto University Graduate School of Medicine, Kyoto, Japan.
5
Department of Pharmacology, Kansai Medical University, Osaka, Japan.
6
Division of Laboratory Animal Science, Research Center for Bioscience and Technology, Tottori University, Tottori, Japan.
7
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Abstract

Epidemiological findings indicate that acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD), although the molecular mechanism remains unclear. Genetic fate mapping demonstrated that nephrons, functional units in the kidney, are repaired by surviving nephrons after AKI. However, the cell population that repairs damaged nephrons and their repair capacity limitations remain controversial. To answer these questions, we generated a new transgenic mouse strain in which mature proximal tubules, the segment predominantly damaged during AKI, could be genetically labelled at desired time points. Using this strain, massive proliferation of mature proximal tubules is observed during repair, with no dilution of the genetic label after the repair process, demonstrating that proximal tubules are repaired mainly by their own proliferation. Furthermore, acute tubular injury caused significant shortening of proximal tubules associated with interstitial fibrosis, suggesting that proximal tubules have a limited capacity to repair. Understanding the mechanism of this limitation might clarify the mechanism of the AKI-to-CKD continuum.

KEYWORDS:

acute kidney injury; chronic kidney disease; fibrosis; nephron; regeneration; tubule

PMID:
25664690
DOI:
10.1002/path.4514
[Indexed for MEDLINE]

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