scholarly journals WNT/β-Catenin Signaling Is Required for Integration of CD24+Renal Progenitor Cells into Glycerol-Damaged Adult Renal Tubules

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Zhao Zhang ◽  
Diana M. Iglesias ◽  
Rachel Corsini ◽  
LeeLee Chu ◽  
Paul Goodyer
Keyword(s):  
Progenitor Cells ◽  
Kidney Injury ◽  
Perinatal Period ◽  
Renal Tubules ◽  
Adult Mice ◽  
Renal Progenitor Cells ◽  
Nephron Progenitor ◽  
Canonical Wnt ◽  
Renal Progenitor

During development, nephron progenitor cells (NPC) are induced to differentiate by WNT9b signals from the ureteric bud. Although nephrogenesis ends in the perinatal period, acute kidney injury (AKI) elicits repopulation of damaged nephrons. Interestingly, embryonic NPC infused into adult mice with AKI are incorporated into regenerating tubules. Since WNT/β-catenin signaling is crucial for primary nephrogenesis, we reasoned that it might also be needed for the endogenous repair mechanism and for integration of exogenous NPC. When we examined glycerol-induced AKI in adult mice bearing aβ-catenin/TCF reporter transgene, endogenous tubular cells reexpressed the NPC marker, CD24, and showed widespreadβ-catenin/TCF signaling. We isolated CD24+cells from E15 kidneys of mice with the canonical WNT signaling reporter. 40% of cells responded to WNT3ain vitroand when infused into glycerol-injured adult, the cells exhibitedβ-catenin/TCF reporter activity when integrated into damaged tubules. When embryonic CD24+cells were treated with aβ-catenin/TCF pathway inhibitor (IWR-1) prior to infusion into glycerol-injured mice, tubular integration of cells was sharply reduced. Thus, the endogenous canonicalβ-catenin/TCF pathway is reactivated during recovery from AKI and is required for integration of exogenous embryonic renal progenitor cells into damaged tubules. These events appear to recapitulate the WNT-dependent inductive process which drives primary nephrogenesis.

scholarly journals Renal Progenitor Cells Have Higher Genetic Stability and Lower Oxidative Stress than Mesenchymal Stem Cells during In Vitro Expansion

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Elís Rosélia Dutra de Freitas Siqueira Silva ◽  
Napoleão Martins Argôlo Neto ◽  
Dayseanny de Oliveira Bezerra ◽  
Sandra Maria Mendes de Moura Dantas ◽  
Lucilene dos Santos Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Dna Damage ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Genetic Stability ◽  
Renal Progenitor Cells ◽  
In Vitro Expansion ◽  
Renal Progenitor

In vitro senescence of multipotent cells has been commonly associated with DNA damage induced by oxidative stress. These changes may vary according to the sources of production and the studied lineages, which raises questions about the effect of growing time on genetic stability. This study is aimed at evaluating the evolution of genetic stability, viability, and oxidative stress of bone marrow mesenchymal stem cells (MSCBMsu) and renal progenitor cells of the renal cortex (RPCsu) of swine (Sus scrofa domesticus) in culture passages. P2, P5, and P9 were used for MSCBMsu and P1, P2, and P3 for RPCsu obtained by thawing. The experimental groups were submitted to MTT, apoptosis and necrosis assays, comet test, and reactive substance measurements of thiobarbituric acid (TBARS), nitrite, reduced glutathione (GSH), and catalase. The MTT test curve showed a mean viability of 1.14±0.62 and 1.12±0.54, respectively, for MSCBMsu and RPCsu. The percentages of MSCBMsu and RPCsu were presented, respectively, for apoptosis, an irregular and descending behavior, and necrosis, ascending and irregular. The DNA damage index showed higher intensity among the MSCBMsu in the P5 and P9 passages (p<0.05). In the TBARS evaluation, there was variation among the lines of RPCsu and MSCBMsu, presenting the last most significant variations (p<0.05). In the nitrite values, we identified only among the lines, in the passages P1 and P2, with the highest averages displayed by the MSCBMsu lineage (p<0.05). The measurement of antioxidant system activity showed high standards, identifying differences only for GSH values, in the RPCsu lineage, in P3 (p<0.05). This study suggests that the maintenance of cell culture in the long term induces lower regulation of oxidative stress, and RPCsu presents higher genetic stability and lower oxidative stress than MSCBMsu during in vitro expansion.

scholarly journals SaO032PAPILLARY RENAL CELL CARCINOMA ORIGINATES FROM A POPULATION OF RENAL PROGENITOR CELLS AND IS PROMOTED BY ACUTE KIDNEY INJURY

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i328-i328
Author(s):  
Anna Peired ◽  
Giulia Antonelli ◽  
Maria Lucia Angelotti ◽  
Alessandro Sisti ◽  
Marco Allinovi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Acute Kidney Injury ◽  
Cell Carcinoma ◽  
Progenitor Cells ◽  
Renal Cell ◽  
Kidney Injury ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

2020 ◽  
Vol 12 (536) ◽  
pp. eaaw6003 ◽  
Author(s):  
Anna Julie Peired ◽  
Giulia Antonelli ◽  
Maria Lucia Angelotti ◽  
Marco Allinovi ◽  
Francesco Guzzi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Renal Cell ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Lineage Tracing ◽  
Cell Of Origin ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.

Retinoic Acid Benefits Glomerular Organotypic Differentiation from Adult Renal Progenitor Cells In Vitro

2021 ◽  
Author(s):  
Rita Sobreiro-Almeida ◽  
Maria Elena Melica ◽  
Laura Lasagni ◽  
Paola Romagnani ◽  
Nuno M. Neves
Keyword(s):  
Retinoic Acid ◽  
Progenitor Cells ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

scholarly journals Acute and chronic glomerular damage is associated with reduced CD133 expression in urinary extracellular vesicles

2020 ◽  
Vol 318 (2) ◽  
pp. F486-F495 ◽  
Author(s):  
Veronica Dimuccio ◽  
Licia Peruzzi ◽  
Maria Felice Brizzi ◽  
Enrico Cocchi ◽  
Fabrizio Fop ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Extracellular Vesicles ◽  
Cell Damage ◽  
Characteristic Curve ◽  
Chronic Glomerulonephritis ◽  
Acute Glomerulonephritis ◽  
Renal Progenitor Cells ◽  
Glomerular Damage ◽  
Renal Progenitor

Extracellular vesicles released into urine (uEVs) can represent interesting biomarkers of renal cell damage. CD133, a stem/progenitor cell marker expressed by renal progenitor cells, is highly expressed in uEVs of healthy individuals. In the present study, we evaluated the level of CD133 in the uEVs of patients with acute and chronic glomerular damage by cytofluorimetric analysis. The level of CD133+ uEVs was significantly decreased in pediatric patients with acute glomerulonephritis during the acute phase of renal damage, while it was restored after the subsequent recovery. A similar decrease was also observed in patients with chronic glomerulonephritis. Moreover, CD133+ uEVs significantly declined in patients with type 2 diabetes, used as validation group, with the lowest levels in patients with albuminuria with diabetic nephropathy. Indeed, receiver-operating characteristic curve analysis indicates the ability of CD133+ uEV values to discriminate the health condition from that of glomerular disease. In parallel, a significant decrease of CD133 in renal progenitor cells and in their derived EVs was observed in vitro after cell treatment with a combination of glucose and albumin overload, mimicking the diabetic condition. These data indicate that the level of CD133+ uEVs may represent an easily accessible marker of renal normal physiology and could provide information on the “reservoir” of regenerating cells within tubules.

BMP-2 induces a profibrotic phenotype in adult renal progenitor cells through Nox4 activation

2012 ◽  
Vol 303 (1) ◽  
pp. F23-F34 ◽  
Author(s):  
Simona Simone ◽  
Carmela Cosola ◽  
Antonia Loverre ◽  
Marica Cariello ◽  
Fabio Sallustio ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Protein Expression ◽  
Progenitor Cells ◽  
Smooth Muscle Actin ◽  
Graft Function ◽  
Renal Progenitor Cells ◽  
Bmp Receptors ◽  
Renal Progenitor

Adult renal progenitor cells (ARPCs) isolated from the human kidney may contribute to repair featuring acute kidney injury (AKI). Bone morphogenetic proteins (BMPs) regulate differentiation, modeling, and regeneration processes in several tissues. The aim of this study was to evaluate the biological actions of BMP-2 in ARPCs in vitro and in vivo. BMP-2 was expressed in ARPCs of normal adult human kidneys, and it was upregulated in vivo after delayed graft function (DGF) of renal transplantation, a condition of AKI. ARPCs expressed BMP receptors, suggesting their potential responsiveness to BMP-2. Incubation of ARPCs with this growth factor enhanced reactive oxygen species (ROS) production, NADPH oxidase activity, and Nox4 protein expression. In vivo, Nox4 was localized in BMP-2-expressing CD133+ cells at the tubular level after DGF. BMP-2 incubation induced α-smooth muscle actin (SMA), collagen I, and fibronectin protein expression in ARPCs. Moreover, α-SMA colocalized with CD133 in vivo after DGF. The oxidative stimulus (H2O2) induced α-SMA expression in ARPCs, while the antioxidant N-acetyl-cysteine inhibited BMP-2-induced α-SMA expression. Nox4 silencing abolished BMP-2-induced NADPH oxidase activation and myofibroblastic induction. We showed that 1) ARPCs express BMP-2, 2) this expression is increased in a model of AKI; 3) BMP-2 may induce the commitment of ARPCs toward a myofibroblastic phenotype in vitro and in vivo; and 4) this profibrotic effect is mediated by Nox4 activation. Our findings suggest a novel mechanism linking AKI with progressive renal damage.

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