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Possible Mechanisms of Kidney Repair

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Possible Mechanisms of Kidney Repair

Paola Romagnani et al. Fibrogenesis Tissue Repair.

Abstract

In most adult epithelia the process of replacing damaged or dead cells is maintained through the presence of stem/progenitor cells, which allow epithelial tissues to be repaired following injury. Existing evidence strongly supports the presence of stem cells in the adult kidney. Indeed, recent findings provide evidence in favour of a role for intrinsic renal cells and against a physiological role for bone marrow-derived stem cells in the regeneration of renal epithelial cells. In addition, recent studies have identified a subset of CD24+CD133+ renal progenitors within the Bowman's capsule of adult human kidney, which provides regenerative potential for injured renal epithelial cells. Intriguingly, CD24+CD133+ renal progenitors also represent common progenitors of tubular cells and podocytes during renal development. Chronic injury causes dysfunction of the tubular epithelial cells, which triggers the release of fibrogenic cytokines and recruitment of inflammatory cells to injured kidneys. The rapid interposition of scar tissue probably confers a survival advantage by preventing infectious microorganisms from invading the wound, but prevents subsequent tissue regeneration. However, the existence of renal epithelial progenitors in the kidney suggests a possible explanation for the regression of renal lesions which has been observed in experimental animals and even in humans. Thus, manipulation of the wound repair process in order to shift it towards regeneration will probably require the ability to slow the rapid fibrotic response so that renal progenitor cells can allow tissue regeneration rather than scar formation.

Figures

Figure 1
Figure 1
CD24+CD133+ renal progenitors localize at the urinary pole of the Bowman's capsule in adult human kidneys. (A) Triple-label immunofluorescence for CD133, (green), CD24 (red) and β1 integrin (blue) showing that in a mature glomerulus, co-expression of CD133 and CD24 characterizes a subset of cells in the Bowman's capsule (white) localized at the urinary pole (UP). AA = afferent arteriola. Objective 20×. (B) High power magnification of a triple-label immunofluorescence for CD133, (green), CD24 (red) and CD106 (blue) in a subset of cells in the Bowman's capsule (white). Sections were stained as previously reported [15].
Figure 2
Figure 2
Hypothetical diagram for kidney regeneration by different types of renal and extrarenal progenitors. CD24+CD133+ renal progenitors (red) are localized at the urinary pole and are in close contiguity with podocytes (green) at one extremity (the vascular stalk) and with tubular renal cells (yellow) at the other extremity. A transitional cell population (red/green) displays features of either renal progenitors (red) or podocytes (green) and localizes between the urinary pole and the vascular pole. At the vascular stalk of the glomerulus, the transitional cells are localized in close continuity with cells that lack progenitor markers, but exhibit the podocyte markers and the phenotypic features of differentiated podocytes (green). On the opposite side, at the urinary pole, transitional cells (red/yellow) with a mixed phenotype between tubular cells (yellow) and progenitor cells (red). The directions of differentiation is indicated by the arrows (modified from [24]).
Figure 3
Figure 3
Hypothetical diagram for kidney fibrosis. Chronic injury causes dysfunction of the tubular epithelial cells, which triggers release of fibrogenic cytokines and recruitment of inflammatory cells to injured kidneys. Myelo-monocytic cells recruited from the bone marrow produce TGF-β1 in injured kidneys. In turn, TGF-β1 induces activation of collagen-producing cells, which mostly arise from kidney resident cells through epithelial-mesenchymal transition (modified [24]).

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