Review
Renal progenitors in non-diabetic and diabetic nephropathies

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Chronic kidney disease represents a major health problem worldwide. Although the kidney has the ability to repopulate structures that have sustained some degree of injury, the mechanisms underlying its regenerative capacity have been unclear. Recent evidence now supports the existence of a renal progenitor system able to replace podocytes and tubular cells, localized within the urinary pole of Bowman's capsule and along the tubule. Altered growth or differentiation of renal progenitors has been reported in several renal disorders including diabetic nephropathy. Pharmacological modulation of renal progenitor growth or differentiation can enhance kidney regeneration, suggesting that treatments aimed at reversing kidney injury are possible. Renal progenitors may represent a novel target in diabetic nephropathy and other kidney disorders.

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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