Nephron Experimental Nephrology最新文献

Background: Plants are characterized by indeterminate post-embryonic development that is evident, for example, in the continuous branching of shoots and roots. High competence to regenerate tissues is another consequence of such intrinsic developmental plasticity in plants. It has been suggested that specialized groups of cells within plant meristems should be compared to stem cells in animals, but the utility of this label in the context of post-embryonic plant development and regeneration is often debated.

Summary: This paper is organized into 3 short sections, where (a) key observations and experimental results on tissue regeneration in plants - mainly in the model system Arabidopsis thaliana, (b) stem cell activity and (c) their role in regeneration are described. The main focus is maintained on the critical aspects of defining stem cell-ness in plants, particularly in the context of tissue regeneration. A number of recent excellent reviews are cited throughout the text to give the reader the appropriate tools to dig deeper into the various stimulating topics introduced here.

Key messages: Despite the remarkable somatic developmental plasticity characterizing post-embryonic development in plants, use of the classic concept of stem cells has been imported from the animal literature with the goal of facilitating our understanding and description of plant developmental processes. It is not clear if this is the case, especially in light of the recent experimental results on root regeneration in Arabidopsis mutants.

Background: Kidney regeneration is currently gaining considerable attention in place of kidney dialysis as the ultimate therapeutic strategy for renal failure. However, because of anatomical complications, the kidney is believed to be the hardest organ to regenerate. Such a complicated organ is virtually impossible to imagine being completely rebuilt de novo from stem cells. Nevertheless, several research groups are attempting this large challenge.

Summary: There are 4 major strategies for de novo kidney regeneration from stem cells. These strategies include the use of: (i) a decellularized cadaveric scaffold, (ii) blastocyst decomplementation, (iii) a nephrogenic niche for growing a xeno-embyro, and (iv) self-assembly potential. All of these strategies may be applicable in the clinical setting, but a substantial preparation period appears to be required.

Key messages: Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, trials provide hope for dialysis patients and kidney regeneration is expected to be a reality in the future.

Background: Millions of people are affected by irreversible loss of renal function and thus by a significantly increased cardiovascular risk. In this context, the parietal epithelial cells (PECs) of the glomerulus have attracted increasing attention in recent years. So far, they have been ascribed 2 major functions: (1) PECs may act as intrinsic progenitor cells to replenish podocytes and/or proximal tubular cells and (2) a major role of PECs has been proposed in 2 glomerular disease entities [i.e. rapidly progressing glomerulonephritis (RPGN) and focal and segmental glomerulosclerosis (FSGS)].

Summary: In this review, the major recent findings regarding the role of PECs in glomerular disease are summarized. Novel transgenic technologies have allowed major advances, in particular cell fate-tracing studies.

Key messages: Using these methods, it could be established that the proliferating cells in Bowman's space, which are characteristically found in RPGN, are derived almost exclusively from the glomerular epithelium - primarily PECs. Similarly, it could be shown that PECs participate in the formation of sclerotic lesions in FSGS. Since PECs deposit their characteristic extracellular matrix within these lesions, they likely contribute to the sclerotic process. A common feature of both diseases is that PECs are 'activated', i.e. PECs acquire a larger cytoplasm and nucleus and show increased migration and/or proliferation. Activated PECs can be identified by de novo expression of the marker CD44. These findings broaden our understanding of the pathogenesis of 2 different glomerular diseases: RPGN and FSGS. The participation of activated PECs in both diseases identifies these cells as prime pharmacological targets to develop more specific therapies for both diseases.

Background: Cisplatin (CDDP)-induced acute kidney injury (AKI) involves pro-inflammatory responses, apoptosis of renal tubular epithelial cells and vascular damage. AKI increases the risk of chronic kidney disease. Relaxin (RLX) has anti-apoptotic and anti-fibrosis properties. The aim of this study was to investigate the effects of RLX on CDDP-induced nephrotoxicity.

Methods: We investigated the mitigating effects of RLX based on the etiopathology of AKI induced by CDDP, and also the anti-fibrotic effect of RLX on renal fibrosis after AKI. In the short-term experiments, rats were divided into the control group, CDDP group, and CDDP+RLX group. In the latter group, RLX was infused for 5 or 14 days using an implanted osmotic minipump. CDDP was injected intraperitoneally (6 mg/kg) after RLX or saline infusion. At 5 and 14 days post-CDDP, the kidneys were removed for analysis. The effect of RLX on renal fibrosis after AKI was evaluated at 6 weeks post-CDDP.

Results: In short-term experiments, CDDP transiently increased plasma creatinine and blood urea nitrogen with peaks at day 5, and RLX prevented such rises. Semiquantitative analysis of the histological lesions indicated marked structural damage and apoptotic cells in the CDDP group, with the lesions being reduced by RLX treatment. Overexpression of Bax, interleukin-6 and tumor necrosis factor-α observed in the kidneys of the CDDP group was reduced in the CDDP+RLX group. In the long-term experiments, RLX significantly reduced renal fibrosis compared with the CDDP group.

Conclusions: The results suggested that RLX provided protection against CDDP-induced AKI and subsequent fibrosis by reducing apoptosis and inflammation.

The incidence of acute kidney injury due to ischaemia-reperfusion injury (IRI) is rising but effective treatments and preventative approaches are currently lacking. IRI is also an inevitable consequence of kidney transplantation and significantly contributes to delayed graft function. Heat-shock proteins (Hsps) are highly conserved and ubiquitously expressed molecular chaperones that help maintain and restore normal cellular function in the kidney following IRI. Hsp70 is one of the most frequently studied Hsps because of potential cytoprotective properties and attractiveness as a therapeutic target. However, the protective properties of Hsp70 in renal IRI are not fully understood and putative modes of protection include correction of protein conformation, cytoskeletal stabilisation, anti-inflammatory effects, requirement in autophagy, anti-apoptotic properties, influence over macrophage phenotype and stimulation of regulatory T cells. Significant clinical interest has been generated about the possibility of applying pharmacological agents to induce Hsp70 and prevent renal IRI, but prior to this, an increased mechanistic understanding of the protective nature of Hsp70 is needed. In particular, further investigation of Hsp expression on inflammatory cell behaviour is required as this could lead to the development of new therapeutic strategies for enhancing recovery following renal IRI and broaden the range of these therapies to a wider group of patients.

Background: Wnt5a is important for the development of various organs and postnatal cellular function. Little is known, however, about the role of Wnt5a in kidney development, although WNT5A mutations were identified in patients with Robinow syndrome, a genetic disease which includes developmental defects in kidneys. Our goal in this study was to determine the role of Wnt5a in kidney development.

Methods: Whole-mount in situ hybridization was used to establish the expression pattern of Wnt5a during kidney development. Zebrafish with wnt5a knockdown and Wnt5a global knockout mice were used to identify kidney phenotypes.

Results: In zebrafish, wnt5a knockdown resulted in glomerular cyst formation and dilated renal tubules. In mice, Wnt5a global knockout resulted in pleiotropic, but severe, kidney phenotypes, including agenesis, fused kidney, hydronephrosis and duplex kidney/ureter.

Conclusions: Our data demonstrated the important role of Wnt5a in kidney development. Disrupted Wnt5a resulted in kidney cysts in zebrafish and pleiotropic abnormal kidney development in mice.

Background: Renal ischemia-reperfusion (IR) injury is a frequent cause of acute kidney injury, which results in high morbidity and mortality. Inflammation is an important factor that is involved in kidney repair after renal IR injury. IL-10 is a potent anti-inflammatory cytokine that inhibits inflammatory pathways, but the role of IL-10 in repairing renal IR injury is not known. Here, we investigated the role of IL-10 in kidney repair after renal IR injury.

Methods: We used an IL-10(-/-) mouse model and examined the serologic and histomorphology of kidney after IR injury. We also measured ki67, TNF-α, IL-6, and macrophages with immunohistochemistry or Western blotting.

Results: There was a greater increase in serum creatinine in IL-10(-/-) mice than in wild-type (WT) mice. And compared with WT mice, IL-10(-/-) mice had increased histologic renal injury and decreased proliferation. Moreover, the expression of TNF-α, IL-6 and macrophages was clearly increased in IL-10(-/-) mice compared with the WT mice.

Conclusion: These data reveal an important role for IL-10 in the improvement of renal IR injury, acting through suppression of inflammatory mediators, and that IL-10 would be a crucial target for the treatment of IR injury.