Trends in Endocrinology & Metabolism
ReviewRenal progenitors in non-diabetic and diabetic nephropathies
Section snippets
Chronic kidney disease and diabetic nephropathy
Chronic kidney disease (Box 1) represent a major global health problem, and approximately 600 million people are affected worldwide [1]. These individuals are at increased risk of death and progression to end-stage renal disease (ESRD), which requires dialysis or kidney transplant, with costs that cannot be afforded by most developing countries and that are also becoming very problematic for wealthier nations 1, 2. Diabetes is the most common single cause of ESRD in the US and Europe [3]. In
Kidney regeneration
In recent years several studies performed in animal models of diabetic and non-diabetic nephropathy demonstrated that treatment with angiotensin converting enzyme (ACE) inhibitors, angiotensin-II type 1 receptor blockers, or their combination not only prevents progressive renal damage but also promotes regression of glomerulosclerosis 6, 7, 8, 9, 10, 11, 12, 13. In rats with advanced nephropathy, administration of high-dose ACE inhibitor reduced the volume of sclerosis in most glomeruli, while
Renal progenitors in non-diabetic and diabetic nephropathies
Several results suggest that an altered growth and/or differentiation ability of renal progenitors may also be responsible for the generation of disorders, a concept that is widely accepted in several stem-cell systems 43, 44. Indeed, in collapsing glomerulopathy or crescentic glomerulonephritis, two glomerular disorders characterized by an unfavorable prognosis and rapid progression towards glomerulosclerosis and ESRD, an abnormal response to podocyte injury causes aberrant renal progenitor
Concluding remarks
The kidney has long been considered as an organ incapable of true regeneration. However, renal injuries can at least partially heal, and the integrity as well as functionality of the injured portion of the nephron can be restored. In the past few years, studies performed in the kidney have supported the existence of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells. Renal progenitors were first identified in human, where they localize within the
Acknowledgments
This manuscript is supported by a European Research Council (ERC) Starting Grant under the European Commission (EC) Seventh Framework Programme (FP7/2007–2013), ERC grant number 205027, by the EC Seventh Framework Programme (FP7/2012–2016), by the Tuscany Ministry of Health (Bando Salute 2009), by the Italian Ministry of Health, and by the Associazione Italiana per la Ricerca sul Cancro. Preparation of the manuscript was also supported in part by the ERC-2010-7 AdG-268632 RESET Grant.
Glossary
- Genetic lineage-tracing
- a genetic strategy to detect stem or progenitor cells and their derived progeny that is considered as a direct proof of their identification. In this technique, a cell is permanently tagged by introducing a reporter gene under the control of a cell-specific promoter. The specific marker is transmitted to all the progeny of the cell even when the phenotype of the derived progeny is different and stem/progenitor cell markers are lost. This allows the detection of the
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Cited by (56)
Great potential of renal progenitor cells in kidney: From the development to clinic
2024, Experimental Cell ResearchRole of the P2X7 receptor in the pathogenesis of type 2 diabetes and its microvascular complications
2019, Current Opinion in PharmacologyCitation Excerpt :Even mild episodes of AKI, with small and transient increase in serum creatinine, might result in CKD, especially in the presence of risk factors such as diabetes. This picture is made even more complex by the fact that the regenerative potential of tubular progenitors is limited and might be reduced in diabetes [40]. Treatment with Renin-Angiotensin System (RAS) blockers increases susceptibility to renal ischemia, and repeated, even subclinical episodes might progressively reduce GFR.
Principles of Kidney Regeneration
2017, Kidney Transplantation, Bioengineering, and Regeneration: Kidney Transplantation in the Regenerative Medicine EraRegenerative medicine in kidney disease
2016, Kidney InternationalCitation Excerpt :As well as progenitors involved in tubular turnover, there is also evidence for progenitors with overlapping protein signatures that can contribute to the turnover of podocytes within the glomerulus.26,27 Some view the RPC population of the postnatal renal tubules as potentially representing a retained tubular progenitor, in part based on expression of markers such as Pax2 seen in the developing organ.24 Although it is clear that RPCs do not have a capacity to regenerate an entire nephron, the concept is that each segment might contain a distinct tubular progenitor able to selectively contribute to repair via differential proliferation in response to injury.