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Tubular regeneration: when can the kidney regenerate from injury and what turns failure into success?

Johansson, Martin LU (2014) In Nephron. Experimental Nephrology 126(2). p.76-81
Abstract
Background: The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of... (More)
Background: The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of the skin and intestine, where stem cells maintain a continuous flow of new cells from designated niches. Summary: This review discusses the classical concept of renal regeneration, i.e. stochastically surviving cells undergoing dedifferentiation (or epithelial-mesenchymal transition) followed by replenishment of the tubular epithelium. Furthermore however, this view has recently been challenged by the concept of organ-confined stem/progenitor cells, bone marrow-derived stem cells, or mesenchymal stem cells taking part in the regenerative events. Whereas results from animal models support the classical view, morphologically distinct cells have been demonstrated in human kidneys, requiring interpretation. This review presents some of the previous work and techniques and highlights issues that need to be reconciled. Key Messages: In adult humans, the kidney tubules contain scattered cells with a distinct set of markers and properties, such as increased robustness during tubular damage. These cells may be induced by injury or represent a resident progenitor cell pool. To date, animal studies using lineage-tracing methods argue for an inductive scenario. In humans, the situation is less clear and one might speculate that the cellular heterogeneity might reflect elements of cellular reprogramming to a progenitor-like state, perhaps by induction. Due to intense investigational efforts, however, a scientific consensus may soon be reached, which will benefit further research. © 2014 S. Karger AG, Basel. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nephron. Experimental Nephrology
volume
126
issue
2
pages
76 - 81
publisher
Karger
external identifiers
  • pmid:24854645
  • wos:000336239500010
  • scopus:84901405183
ISSN
1660-2129
DOI
10.1159/000360671
language
English
LU publication?
yes
id
19e0b171-e831-4d29-b191-2fd6356f5f9f (old id 4452657)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24854645?dopt=Abstract
date added to LUP
2014-06-06 20:21:13
date last changed
2017-01-22 03:41:13
@article{19e0b171-e831-4d29-b191-2fd6356f5f9f,
  abstract     = {Background: The most common intrarenal cause for acute kidney injury/renal failure is tubular damage. The kidney tubules are arranged as compartments of cellular mosaics to perform their functions, and at rest almost a fifth of the human ATP consumption is allotted to the reabsorption of substances from the filtrate, rendering especially the proximal tubules highly sensitive to oxygen and/or nutrient deprivation. Normally mitotically quiescent, the tubular epithelium shows a brisk regenerative response following injury if supportive care is offered, allowing functional restoration. Despite this, the cellular machinery behind the regenerative capacity is still not unequivocally defined. This is at odds with other epithelia such as those of the skin and intestine, where stem cells maintain a continuous flow of new cells from designated niches. Summary: This review discusses the classical concept of renal regeneration, i.e. stochastically surviving cells undergoing dedifferentiation (or epithelial-mesenchymal transition) followed by replenishment of the tubular epithelium. Furthermore however, this view has recently been challenged by the concept of organ-confined stem/progenitor cells, bone marrow-derived stem cells, or mesenchymal stem cells taking part in the regenerative events. Whereas results from animal models support the classical view, morphologically distinct cells have been demonstrated in human kidneys, requiring interpretation. This review presents some of the previous work and techniques and highlights issues that need to be reconciled. Key Messages: In adult humans, the kidney tubules contain scattered cells with a distinct set of markers and properties, such as increased robustness during tubular damage. These cells may be induced by injury or represent a resident progenitor cell pool. To date, animal studies using lineage-tracing methods argue for an inductive scenario. In humans, the situation is less clear and one might speculate that the cellular heterogeneity might reflect elements of cellular reprogramming to a progenitor-like state, perhaps by induction. Due to intense investigational efforts, however, a scientific consensus may soon be reached, which will benefit further research. © 2014 S. Karger AG, Basel.},
  author       = {Johansson, Martin},
  issn         = {1660-2129},
  language     = {eng},
  number       = {2},
  pages        = {76--81},
  publisher    = {Karger},
  series       = {Nephron. Experimental Nephrology},
  title        = {Tubular regeneration: when can the kidney regenerate from injury and what turns failure into success?},
  url          = {http://dx.doi.org/10.1159/000360671},
  volume       = {126},
  year         = {2014},
}