RESUMEN

Renal tubules have potential to regenerate and repair after mild-to-moderate injury. Proliferation of tubular epithelial cells represents the initial step of this reparative process. Although for many years, it was believed that proliferating cells originated from a pre-existing intra-tubular stem cell population, there is now consensus that surviving tubular epithelial cells acquire progenitor properties to regenerate the damaged kidney. Scattered tubular-like cells (STCs) are dedifferentiated adult renal tubular epithelial cells that arise upon injury and contribute to renal self-healing and recovery by replacing lost neighboring tubular epithelial cells. These cells are characterized by the co-expression of the stem cell surface markers CD133 and CD24, as well as mesenchymal and kidney injury markers. Previous studies have shown that exogenous delivery of STCs ameliorates renal injury and dysfunction in murine models of acute kidney injury, underscoring the regenerative potential of this endogenous repair system. Although STCs contain fewer mitochondria than their surrounding terminally differentiated tubular epithelial cells, these organelles modulate several important cellular functions, and their integrity and function are critical to preserve the reparative capacity of STCs. Recent data suggest that the microenviroment induced by cardiovascular risk factors, such as obesity, hypertension, and renal ischemia may compromise STC mitochondrial integrity and function, limiting the capacity of these cells to repair injured renal tubules. This review summarizes current knowledge of the contribution of STCs to kidney repair and discusses recent insight into the key role of mitochondria in modulating STC function and their vulnerability in the setting of cardiovascular disease.

Asunto(s)

Mitocondrias , Regeneración , Humanos , Mitocondrias/metabolismo , Animales , Regeneración/fisiología , Túbulos Renales/metabolismo , Túbulos Renales/patología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/patología , Riñón/metabolismo , Células Epiteliales/metabolismo

RESUMEN

Cell membrane-based nanovesicles (CMNVs) play pivotal roles in biomolecular transportation in living organisms and appear as attractive bioinformed nanomaterials for theranostic applications. However, the current surface-engineering technologies are limited in flexibility and orthogonality, making it challenging to simultaneously display multiple different ligands on the CMNV surface in a precisely controlled manner. Here, we developed a DNA scaffold-programmed approach to orthogonally engineer CMNVs with versatile ligands. The designed DNA scaffolds can rapidly anchor onto the CMNV surface, and their unique sequences and hybridized properties enable independent control of the loading of multiple different types of biomolecules on the CMNVs. As a result, the orthogonal engineering of CMNVs with a renal targeted peptide and a therapeutic protein at controlled ratios demonstrated an enhanced renal targeting and repair potential in vivo. This study highlights that a DNA scaffold-programmed platform can provide a potent means for orthogonal and flexible surface engineering of CMNVs for diverse therapeutic purposes.

RESUMEN

Chronic Kidney Disease (CKD) is increasingly recognized as a global public health issue. Diabetic nephropathy (DN), also known as diabetic kidney disease, is a leading cause of CKD. Regenerative medicine strategy employing nephron progenitor cells (NPCs) is worthy of consideration as an alternative to shortage of donor organs for kidney transplantation. In previous study, we successfully generated induced NPCs (iNPCs) from human urine-derived cells that resembled human embryonic stem cell-derived NPCs. Here, we aimed to investigate the therapeutic potential of iNPCs in DN animal model. The results revealed the therapeutic effect of iNPCs as follows: (1) diminished glomerular hypertrophy, (2) reduced tubulointerstitial fibrosis, (3) low blood urea nitrogen, serum creatinine and albuminuria value, (4) decreased inflammation/fibrosis, (5) enhanced renal regeneration and (6) confirmed safety. This study demonstrates that human iNPCs have a therapeutic potential as a cell source for transplantation in patients with kidney diseases.

Asunto(s)

Diabetes Mellitus , Nefropatías Diabéticas , Insuficiencia Renal Crónica , Animales , Creatinina , Diabetes Mellitus/patología , Nefropatías Diabéticas/tratamiento farmacológico , Fibrosis , Humanos , Riñón/patología , Ratones , Nefronas , Insuficiencia Renal Crónica/patología , Células Madre

RESUMEN

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs) in the first line defense system of our bodies; they are widely expressed on leukocytes and kidney epithelial cells. Infections due to pathogens or danger signals from injured tissues often activate several TLRs and these receptors mediate their signal transduction through the activation of transcription factors that regulate the expression of cytokine interleukin-1ß (IL-1ß), type I interferons (IFNs), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) dependent cytokines and chemokines. Acute kidney injury (AKI) involves early Toll-like receptors driven immunopathology, while resolution of inflammation is needed for rapid regeneration of injured tubular cells. Despite their well known function in the progression of inflammation; interestingly, activation of TLRs also has been implicated in renal epithelial repair through the induction of certain interleukins and improvement in autophagy mechanism. Studies have found that although the blockade of TLRs during the early injury phase of renal tissues prevented tubular necrosis, suppression of interleukins production and impaired kidney regeneration due to their blockade has been observed during the healing phase of tissue. Taken together, these results suggest that the two danger response programs of renal cells i.e. renal inflammation and regeneration may link at the level of TLRs. This review aims to emphasize on the role of TLRs signaling in different acute kidney injury phases. Understanding of these pathways may turn out to be effective as therapeutic option for kidney diseases.

RESUMEN

Acute kidney injury (AKI) is a clinical condition that is associated with high morbidity and mortality. Inflammation is reported to play a key role in AKI. Although the M2 macrophages exhibit antimicrobial and anti-inflammatory activities, their therapeutic potential has not been evaluated for AKI. This study aimed to investigate the protective effect of peritoneal M2 macrophage transplantation on AKI in mice. The macrophages were isolated from peritoneal dialysates of mice. The macrophages were induced to undergo M2 polarization using interleukin (IL)-4/IL-13. AKI was induced in mice by restoring the blood supply after bilateral renal artery occlusion for 30 minutes. The macrophages were injected into the renal cortex of mice. The changes in renal function, inflammation and tubular proliferation were measured. The M2 macrophages were co-cultured with the mouse primary proximal tubular epithelial cells (PTECs) under hypoxia/reoxygenation conditions in vitro. The PTEC apoptosis and proliferation were analysed. The peritoneal M2 macrophages effectively alleviated the renal injury and inflammatory response in mice with ischaemia-reperfusion injury (IRI) and promoted the PTEC proliferation in vivo and in vitro. These results indicated that the peritoneal M2 macrophages ameliorated AKI by decreasing inflammatory response and promoting PTEC proliferation. Hence, the peritoneal M2 macrophage transplantation can serve as a potential cell therapy for renal diseases.

Asunto(s)

Lesión Renal Aguda/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Macrófagos Peritoneales/trasplante , Daño por Reperfusión/terapia , Animales , Apoptosis/fisiología , Proliferación Celular/fisiología , Supervivencia Celular , Células Cultivadas , Técnicas de Cocultivo , Inflamación/patología , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obstrucción de la Arteria Renal , Cicatrización de Heridas/fisiología

RESUMEN

Previous studies have shown that cGMP increases mitochondrial biogenesis (MB). Our laboratory has determined that formoterol and LY344864, agonists of the ß2-adrenergic receptor and 5-HT1F receptor, respectively, signal MB in a soluble guanylyl cyclase (sGC)-dependent manner. However, the pathway between cGMP and MB produced by these pharmacological agents in renal proximal tubule cells (RPTCs) and the kidney has not been determined. In the present study, we showed that treatment of RPTCs with formoterol, LY344864, or riociguat, a sGC stimulator, induces MB through protein kinase G (PKG), a target of cGMP, and p38, an associated downstream target of PKG and a regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in RPTCs. We also examined if p38 plays a role in PGC-1α phosphorylation in vivo. Administration of l-skepinone, a potent and specific inhibitor of p38α and p38ß, to naïve mice inhibited phosphorylated PGC-1α localization in the nuclear fraction of the renal cortex. Taken together, we demonstrated a pathway, sGC/cGMP/PKG/p38/PGC-1α, for pharmacological induction of MB and the importance of p38 in this pathway.

Asunto(s)

Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Riñón/enzimología , Mitocondrias/metabolismo , Biogénesis de Organelos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Carbazoles/farmacología , Células Cultivadas , Proteínas Quinasas Dependientes de GMP Cíclico/antagonistas & inhibidores , Dibenzocicloheptenos/farmacología , Activación Enzimática , Activadores de Enzimas/farmacología , Femenino , Fluorobencenos/farmacología , Fumarato de Formoterol/farmacología , Riñón/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Conejos , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores

RESUMEN

Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic option for limiting chronic kidney disease progression. Conditioned medium (CM) containing bioactive compounds could convey similar benefits, avoiding the potential risks of cell therapy. This study compared the efficacy of nonrenal and renal cell-based therapy with the corresponding CM in rats with renal mass reduction (RMR). Infusions of human kidney stromal cells (kPSCs) and CM-kPSCs, but not umbilical cord (uc) MSCs or CM-ucMSCs, reduced proteinuria and preserved podocyte number and nephrin expression in RMR rats. Glomerular fibrosis, microvascular rarefaction, and apoptosis were reduced by all treatments, while the peritubular microvascular loss was reduced by kPSCs and CM-kPSCs treatment only. Importantly, kPSCs and CM-kPSCs reduced NG2-positive pericytes, and all therapies reduced α-smooth muscle actin expression, indicating reduced myofibroblast expansion. Treatment with kPSCs also significantly inhibited the accumulation of ED1-positive macrophages in the renal interstitium of RMR rats. These findings demonstrate that the CM of ucMSCs and kPSCs confers similar renoprotection as the cells. kPSCs and CM-kPSCs may be superior in attenuating chronic renal injury as a cell source.

Asunto(s)

Insuficiencia Renal Crónica/fisiopatología , Células del Estroma/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Ratas

RESUMEN

Renal failure is one of the most important causes of mortality and morbidity all over the world. Acute kidney injury (AKI) is a major clinical problem that affects up to 5% of all hospitalized patients. Although the kidney has a remarkable capacity for regeneration after acute injury, the mortality among patients with severe AKI remains dismally high, and in clinical practice, most patients cannot be cured completely and suffer from chronic kidney disease (CKD). Recently, the incidence and prevalence of CKD have increased, largely as a result of the enhanced prevalence of diabetes and obesity. The progressive nature of CKD and the ensuing end-stage renal disease (ESRD) place a substantial burden on global healthcare resources. Currently, dialysis and transplantation remain the only treatment options. Finding new therapeutic methods to fight AKI and CKD remains an ongoing quest. Although the human renal histological structure is complex, stem cell therapies have been applied to repair injured kidneys. The curative effects of mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), and nephron progenitor cells (NPCs) on renal repair have also been reported by researchers. This review focuses on stem cell therapy and mechanisms for renal injury repair.

Asunto(s)

Lesión Renal Aguda/terapia , Tratamiento Basado en Trasplante de Células y Tejidos , Células Madre/citología , Humanos , Riñón , Fallo Renal Crónico/terapia , Nefronas , Insuficiencia Renal Crónica/terapia

RESUMEN

Long-term sequelae of acute kidney injury (AKI) are associated with incomplete recovery of renal function and the development of chronic kidney disease (CKD), which can be mediated by aberrant innate immune activation, mitochondrial pathology, and accumulation of senescent tubular epithelial cells (TECs). Herein, we show that the innate immune receptor Triggering receptor expressed on myeloid cells-1 (TREM-1) links mitochondrial metabolism to tubular epithelial senescence. TREM-1 is expressed by inflammatory and epithelial cells, both players in renal repair after ischemia/reperfusion (IR)-induced AKI. Hence, we subjected WT and TREM1/3 KO mice to different models of renal IR. TREM1/3 KO mice displayed no major differences during the acute phase of injury, but increased mortality was observed in the recovery phase. This detrimental effect was associated with maladaptive repair, characterized by persistent tubular damage, inflammation, fibrosis, and TEC senescence. In vitro, we observed an altered mitochondrial homeostasis and cellular metabolism in TREM1/3 KO primary TECs. This was associated with G2/M arrest and increased ROS accumulation. Further exposure of cells to ROS-generating triggers drove the cells into a stress-induced senescent state, resulting in decreased wound healing capacity. Treatment with a mitochondria anti-oxidant partly prevented the senescent phenotype, suggesting a role for mitochondria herein. In summary, we have unraveled a novel (metabolic) mechanism by which TREM1/3 deficiency drives senescence in TECs. This involves redox imbalance, mitochondrial dysfunction and a decline in cellular metabolic activities. These finding suggest a novel role for TREM-1 in maintaining tubular homeostasis through regulation of mitochondrial metabolic flexibility.

Asunto(s)

Lesión Renal Aguda/patología , Túbulos Renales/citología , Mitocondrias/metabolismo , Receptor Activador Expresado en Células Mieloides 1/genética , Animales , Apoptosis/inmunología , Hipoxia de la Célula/genética , Células Cultivadas , Senescencia Celular/inmunología , Modelos Animales de Enfermedad , Células Epiteliales/citología , Fibrosis/patología , Puntos de Control de la Fase G2 del Ciclo Celular/genética , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oxidación-Reducción , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Receptor Activador Expresado en Células Mieloides 1/deficiencia

RESUMEN

Sepsis-associated acute kidney injury (S-AKI) significantly worsens patient prognosis, and recent evidence suggests that the injury process begins early and may be sustained by therapies used to treat the sepsis (e.g., fluids resuscitation, antibiotics). While efforts to develop less-injurious treatments are making progress, some degree of secondary injury is to be expected. So too is the inevitable nature of organ injury, which is often present at the time the patient seeks medical attention. We recently found that most patients presenting with septic shock and developing AKI had evidence of kidney damage at the time of, or within 24 h of their admission. In such patients, prevention is not a viable option, as injury has already occurred by the time of presentation. Since S-AKI patients are at increased risk of developing chronic kidney disease, a fundamental target for interventions in S-AKI is to prevent fibrosis (maladaptive repair) while stimulating regeneration (proliferation of viable epithelial cells). Using a pathway-agnostic, proliferation-based phenotypic assay, we discovered phenylthiobutanoic acid, a small molecule histone deacetylase inhibitor, that enhances renal recovery and reduces fibrosis in both zebrafish and mouse models of AKI.

Asunto(s)

Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Sepsis/complicaciones , Sepsis/terapia , Lesión Renal Aguda/patología , Animales , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Riñón/patología , Regeneración , Sepsis/patología

RESUMEN

Context: Renal ischaemia reperfusion (I/R) is a common clinical condition with a high morbidity and mortality rate. To date, I/R-induced renal injury remains an ineffective treatment. Objective: We hypothesis that angiogenesis and lymphangiogenesis markers, prospero homeobox-1 (PROX-1) and lymphatic endothelial hyaluronan receptor-1 (LYVE-1), are critical during I/R. Material and methods: Kunming mice were subjected to I/R and observed for the following eight consecutive days. Pathology analysis and protein distribution were detected by H&E staining, immunohistochemistry and immunofluorescence confocal analysis. Results: After I/R treatment, renal pathology was changed. HIF-1α was induced in the early stage and colocalisation with PROX-1 mainly in the renal tubular region, whereas PROX-1 and LYVE-1 were colocalised in the glomerulus of the endothelial region. Conclusions: In this study, we revealed HIF-1α/PROX-1/LVYE-1 axis dynamic changes in different regions after I/R and demonstrated for the first time it activates during I/R repair.

Asunto(s)

Glicoproteínas/metabolismo , Proteínas de Homeodominio/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/patología , Regeneración , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Proteínas Supresoras de Tumor/metabolismo , Animales , Regulación de la Expresión Génica , Riñón/irrigación sanguínea , Riñón/metabolismo , Proteínas de Transporte de Membrana , Ratones , Transporte de Proteínas , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy is a promising strategy for preventing the progression of chronic kidney disease (CKD), with the potential to induce tissue regeneration. In search of the best cellular source we compared, in the rat model of adriamycin (ADR) nephropathy, the regenerative potential of human stromal cells of non-renal origin, such as bone marrow (bm) MSCs and umbilical cord (uc) MSCs, with that of newly discovered stromal cells of renal origin, the kidney perivascular cells (kPSCs) known to exhibit tissue-specific properties. METHODS: The therapeutic effect of repeated infusions of human bmMSCs, ucMSCs, kPSCs (1.5 × 106 cells/rats) or conditioned medium from ucMSCs was studied in athymic rats with ADR-induced nephropathy (7.9 mg/kg). The ability of the three stromal cell populations to engraft the damaged kidney was evaluated by detecting the presence of human nuclear antigenpos cells. Glomerular podocyte loss and endothelial damage, sclerotic lesions and inflammation were assessed at 14 and 28 days. In-vitro experiments with a transwell system were performed to investigate the effects of different stromal cell populations on parietal epithelial cells (PECs) activated or not with albumin or angiotensin II for 24 h. RESULTS: Infusions of non-renal and renal stromal cells resulted in a comparable engraftment into the kidney, in the peritubular areas and around the glomerular structures. All three cell populations limited podocyte loss and glomerular endothelial cell injury, and attenuated the formation of podocyte and PEC bridges. This translated into a reduction of glomerulosclerosis and fibrosis. Human ucMSCs had an anti-inflammatory effect superior to that of the other stromal cells, reducing macrophage infiltration and inducing polarisation towards the M2 macrophage phenotype. Conditioned medium from ucMSCs shared the same renoprotective effects of the cells. Consistent with in-vivo data, bmMSCs and kPSCs, but even more so ucMSCs, limited proliferation, migratory potential and extracellular matrix production of activated PECs, when cultured in a transwell system. CONCLUSIONS: Our data indicate that either non-renal or renal stromal cells induce renal tissue repair, highlighting ucMSCs and their conditioned medium as the most reliable clinical therapeutic tool for CKD patients.

Asunto(s)

Glomeruloesclerosis Focal y Segmentaria/terapia , Supervivencia de Injerto , Trasplante de Células Madre Mesenquimatosas , Insuficiencia Renal Crónica/terapia , Cordón Umbilical/citología , Animales , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Biomarcadores/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Proliferación Celular , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Doxorrubicina/administración & dosificación , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/patología , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/inmunología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/inmunología , Podocitos/efectos de los fármacos , Podocitos/inmunología , Podocitos/patología , Ratas , Ratas Desnudas , Regeneración , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/inmunología , Insuficiencia Renal Crónica/patología , Trasplante Heterólogo , Cordón Umbilical/inmunología , Cordón Umbilical/trasplante

RESUMEN

Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF-R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated.

Asunto(s)

Hipertensión Renal/terapia , Riñón/patología , Litotricia , Nefritis/terapia , Animales , Modelos Animales de Enfermedad , Hipertensión Renal/inducido químicamente , Hipertensión Renal/patología , Masculino , NG-Nitroarginina Metil Éster , Nefritis/inducido químicamente , Nefritis/patología , Ratas , Resultado del Tratamiento

RESUMEN

Ischemic injury to the kidneys is a prevalent clinical problem, contributing importantly to chronic kidney disease. Yet, underlying molecular mechanisms are elusive. To address the possible role of autophagy, we engineered a novel strain of mice harboring a ubiquitously expressed CAG-RFP-EGFP-LC3 transgene. Using this tool, we examined the post-ischemic kidney and detailed the dynamics of renal tubular epithelial autophagy. In addition, we defined the role of MTOR in the resolution of autophagy during epithelial survival and kidney repair.

Asunto(s)

Autofagia/fisiología , Células Epiteliales/citología , Riñón/metabolismo , Daño por Reperfusión , Animales , Autofagia/genética , Modelos Animales de Enfermedad , Riñón/lesiones , Riñón/patología , Ratones

RESUMEN

Objective To compare the impacts of subtotal nephrectomy and ischemiareperfusion injury on renal stem cells and progenitor cells of rats,and to explore the significance of renal stem cells and progenitor cells for renal repair and the possible mechanisms of prognosis in rats with acute renal failure (ARF) or chronic renal failure (CRF).Methods Rats of CRF or ARF model underwent 5/6 nephrectomy or renal artery ligation and repedusion respectively,and rars in control group underwent sham operation.Scr,BUN and 24 hour urine protein were regularly measured.Kidney specimens were obtained at the set time for HE staining and fluorescence staining.Expressions of CD24,CD133 and podocin were detected by immunofluorescence.RT-PCR was performed to quantify the expression of transforming growth factor β1 (TGF-β1),Notch2,hepatocyte growth factor (HGF),bone morphogenetic protein 7 (BMP7) and Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex.Correlation among the expressions of Pax-2 mRNA,podocin mRNA and glomemlosclerosis index were analyzed.Results The rats of two models presented typical ARF or CRF in renal pathology and function.Glomerulosclerosis index in CRF group increased gradually with time,which were (2.34±0.28)％,(25.12±5.67)％,(89.42±12.28)％ and (171.23±32.28)％ at day 14,day 30,day 60 and day 90 respectively.Compared with sham group,the CD24+CD133+ cells of the ARF rats showed no significant change in quantity and distribution,while the CRF rats showed gradual reduction of CD24 +CD133+ cells.The expression of podocin in glomerulus decreased temporarily and recovered finally after ischemiareperfusion injury,but decreased gradually after 5/6 nephrectomy.Compared with sham group,expression of TGF-β1,Notch2 mRNA in renal tissue was increased in CRF group,while the expression of HGF,BMP7 mRNA in renal tissue of ARF group were increased.Between the expression of Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex,there was positive correlation in CRF group,while they both were negatively correlated with glomerulosclerosis index.Conclusions Ischemia-reperfusion injury makes no obvious impairment to renal progenitor cells.Having progressively injured the living environment of renal progenitor cells,subtotal nephrectomy reduces renal progenitor cells,and causes podocytes to repairing incompetently,which may be the main pathogenesis of CRF with poor prognosis.