title: Exploring the origin and limitations of kidney regeneration.
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.
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors: Tomomi
authors: T
authors: Endo
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Jin
authors: J
authors: Nakamura
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Sato
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Misako
authors: M
authors: Asada
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Ryo
authors: R
authors: Yamada
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.|Development II, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan.
authors: Masayuki
authors: M
authors: Takase
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Koji
authors: K
authors: Takaori
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Akiko
authors: A
authors: Oguchi
authors: Development II, Pharmacology Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan.|TMK Project, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Taku
authors: T
authors: Iguchi
authors: Department of Pharmacology, Kansai Medical University, Osaka, Japan.
authors: Atsuko Y
authors: AY
authors: Higashi
authors: Division of Laboratory Animal Science, Research Center for Bioscience and Technology, Tottori University, Tottori, Japan.
authors: Tetsuya
authors: T
authors: Ohbayashi
authors: Department of Pharmacology, Kansai Medical University, Osaka, Japan.
authors: Tomoyuki
authors: T
authors: Nakamura
authors: Department of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors: Eri
authors: E
authors: Muso
authors: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Takeshi
authors: T
authors: Kimura
authors: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Motoko
authors: M
authors: Yanagita
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D005355:Fibrosis / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012038:Regeneration / Q000502:physiology*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: acute kidney injury; chronic kidney disease; fibrosis; nephron; regeneration; tubule