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Renal progenitors: an evolutionary conserved strategy for kidney regeneration

Nature Reviews Nephrology volume 9, pages 137–146 (2013)Cite this article

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Abstract

Following kidney injury, repair can result in functional tissue becoming a patch of cells and disorganized extracellular matrix—a scar—or it can recapitulate the original tissue architecture through the process of regeneration. Regeneration can potentially occur in all animal species and humans. Indeed, the repair of portions of the existing nephron after tubular damage, a response that has been designated classically as cellular regeneration, is conserved in all animal species from the ancestral phases of evolution. By contrast, another type of regenerative response—nephron neogenesis—has been described in lower branches of the animal kingdom, but does not occur in adult mammals. Converging evidence suggests that a renal progenitor system is present in the adult kidney across different stages of evolution, with renal progenitors having been identified as the main drivers of kidney regenerative responses in fish, insects, rodents and humans. In this Review, we describe similarities and differences between the renal progenitor systems through evolution, and propose explanations for how progressive kidney adaptation to environmental changes both required and permitted neonephrogenesis to be given up and for cellular regeneration to be retained as the main regenerative strategy. Understanding the mechanisms that drive renal progenitor growth and differentiation represent the key step for modulating this potential for therapeutic purposes.

Key Points

  • Kidney regeneration occurs in animals and humans following injury through two different strategies: cellular regeneration (in all animals) and nephron neogenesis (in fish, amphibians, reptiles, but not in birds and mammals)

  • Although variable environmental needs across evolution have caused the kidney to take different physical forms and internal organizations, the basic structure of the functional unit of the kidney, the nephron, is mostly conserved

  • A renal progenitor system localized within the nephron that mediates cellular regeneration as well as nephron neogenesis exists in fish, insects, rodents and humans

  • The renal progenitor system consists of stem cells and multiple committed progenitors distributed along the Bowman capsule, the proximal tubule and the distal tubule

  • A shared regenerative strategy based on stem and progenitor cells resulted in the selection of different regenerative solutions in distinct animal classes to allow kidney adaptation to environmental requirements

  • In mammals, enhanced structural complexity related to the appearance of Henle's loop, the division into a cortex and a medulla and an increased number of nephrons resulted in neonephrogenesis being lost and cellular regeneration being retained as the main regenerative strategy

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Figure 1: The kidney through evolution, as it proceeded through a series of successive phases, each marked by the development of a more advanced kidney: the pronephros, mesonephros, and metanephros.
Figure 2: The nephron: an evolutionary link.
Figure 3: Similarities in the localization of renal stem cells and progenitor cells (both depicted in red) in fish, insects and mammalian nephrons.
Figure 4: The morphological events and localization of renal progenitors occurring during nephron development in the adult human kidney.

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Acknowledgements

The authors of this manuscript are supported by the European Research Council (ERC) Starting Grant under the European Community's Seventh Framework Programme (FP7/2007-2013; ERC grant number 205027), the European Community under the European Community's Seventh Framework Programme (FP7/2012-2016; grant number 305436), the Tuscany Ministry of Health (Bando Salute 2009), by the Italian Ministry of Health and by the Associazione Italiana per la Ricerca sul Cancro. The authors are also partially supported by the ERC-2010-7-AdG-268632 RESET Grant.

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  1. Pediatric Nephrology Unit, Meyer Children's Hospital, University of Florence, Viale Pieraccini 24, Florence, 50139, Italy

    Paola Romagnani

  2. Excellence Centre for Research, Transfer and High Education for the development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Morgagni 85, Florence, 50134, Italy

    Laura Lasagni

  3. Mario Negri Institute for Pharmacological Research, Via Stezzano 87, 24126 Bergamo, Italy,

    Giuseppe Remuzzi

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Romagnani, P., Lasagni, L. & Remuzzi, G. Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol 9, 137–146 (2013). https://doi.org/10.1038/nrneph.2012.290

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