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Role of PAX2 gene polymorphisms in Henoch-Schonlein purpura nephritis.

Objective:  To investigate the distribution of polymorphisms in the PAX2 gene in children with Henoch–Schonlein purpura with and without nephritis (HSPN and HSP, respectively), with particular attention to the relationship between PAX2 gene polymorphisms and the development of kidney pathology.

Effect of Stem Cell Factor and Granulocyte-Macrophage Colony-Stimulating Factor-Induced Bone Marrow Stem Cell Mobilization on Recovery from Acute Tubular Necrosis in Rats

Background: Acute tubular necrosis (ATN) is the most common reason for acute kidney injury (AKI), and there is still an absence of effective therapies. Objective: To assess the value of bone marrow cell mobilization by stem cell factor (SCF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy in rats with gentamicin-induced ATN. Methods: ATN was induced in male Sprague–Dawley (SD) rats with five daily high-dose intraperitoneal injections of gentamicin. Subcutaneous injections of SCF and GM-CSF were administered simultaneously and these cytokines were observed on days 2, 5, 10, 17, 24, and 31. Peripheral blood and renal tissue CD34+ cell count, mortality rate, blood urea nitrogen (BUN), serum creatinine (SCr), creatinine clearance rate (CCr), and histopathologic lesion scores were determined. Twelve hours after bone marrow ablation (BMA) by lethal X-ray radiation, specific pathogen-free (SPF) ATN rats were given five daily injections of SCF and GM-CSF. BUN, SCr, and histopathologic lesion scores were evaluated on days 2, 5, and 10. Results: Peripheral blood CD34+ cell count increased significantly in ATN rats between 2 and 10 days after SCF and GM-CSF injection. Mortality was reduced from 34.7% in the ATN group to 18.6% in the ATN+CSF. In addition, cytokines administration significantly decreased SCr and BUN. Moreover, cytokines rapidly ameliorated tubular injury. There was no significant effect on ATN rats after BMA. Conclusions: This study demonstrated that SCF and GM-CSF effectively mobilized bone marrow cells in ATN rats, and cytokines administration partially prevented gentamicin-induced ATN. These results suggest that bone marrow stem cell (BMSC) mobilization may be an effective therapy for ATN.

Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on gentamicin-induced acute tubular necrosis in rats

BackgroundThe subcapsular transplantation of metanephric mesenchymal cells (MMCs) may be a new therapeutic approach for the treatment of acute tubular necrosis (ATN). To investigate this hypothesis and provide evidence for its possible use in the clinic, we evaluated the nephroprotective effects of transplanting MMCs into the renal subcaspsule of rats with ATN induced by gentamicin.MethodsMMCs were expanded in culture. After gentamicin-induced ATN was established, fluorescently-labeled cells were transplanted and traced in kidney tissues by fluorescence microscopy. Serum creatinine (Cr), urea nitrogen (BUN), and N-acetyl-b-D-glucosaminidase (NAG) levels were determined at different time points. Kidney pathology was studied by hematoxylin-eosin staining. Apoptosis was examined by the TUNEL assay.ResultsIn the MMCs-treated group, the mortality rate decreased; BUN, Cr, and NAG levels peaked at 8 days, and were significantly lower than those in the other groups at 11 and 14 days. RIMM-18 cells locally recruited through precise tropism to sites of injury had the ability to migrate into the tubuli from the renal subcapsule. Damage to the cell-treated kidneys was reduced. The pathologic lesion scores of tubular damage reached the highest values at 8 days in the treated kidneys and 11 days in the untreated ones. The apoptotic index showed that the peaks of apoptosis occurred at earlier stages of the injury process in cell-treated than in untreated kidney and thereafter declined in a time-dependent manner.ConclusionThe subcapsular transplantation of MMCs could ameliorate renal function and repair kidney injury.

Angiogenic Effect of Endothelial Progenitor Cells Transfected with Telomerase Reverse Transcriptase on Peritubular Microvessel in Five Out of Six Subtotal Nephrectomy Rats

Renal disease is caused by tubular interstitial injury and renal interstitial fibrosis. Previous studies have shown that transplantation of endothelial progenitor cells (EPCs) may provide an appropriate treatment for repair and reversing renal pathology. However, EPCs are typically low in abundance and have poor replication ability. Therefore, the this study investigated the use of EPCs transfected with the telomerase reverse transcriptase (TERT) in rats that had undergone five out of six subtotal nephrectomy. This study determined the effects of EPC transplantation on renal function, renal interstitial fibrosis, and peritubular capillary angiogenesis. Five groups of rats were investigated: sham group, model group (five out of six subtotal nephrectomy), EPCs-N group (transplantation with EPCs), pZ-TERT-EPCs-N group (transplantation with EPCs transfected with TERT), and pZ-EPCs-N group (transplantation with EPCs transfected with empty plasmid). At weeks 4, 8, and 12 after transplantation, renal function, renal interstitial fibrosis, and peritubular microvessel density (MVD) were investigated. EPCs transfected with TERT gene showed decreased in vitro senescence, apoptosis, and proliferative ability was significantly enhanced (p < 0.05). Furthermore, rat transplanted with EPCs transfected with TERT showed significantly reduced renal interstitial fibrosis and increased endogenous creatinine clearance rate and peritubular MVD (p < 0.05). The transplantation of EPCs expressing TERT into five out of six subtotal nephrectomy rats was shown to improve renal function, reduce loss of peritubular microvessel, and inhibit progression of renal interstitial fibrosis. These studies provide the basis for a potential treatment of renal disease using genetically modified EPCs.

Distribution of infused umbilical cord mesenchymal stem cells in a rat model of renal interstitial fibrosis

Abstract Aims: Stem cell transplantation for the treatment of kidney diseases is dependent on choice of transplant pathway. We evaluated the safety of human umbilical cord mesenchymal stem cells through peripheral infusion and their distribution in a rat model of renal interstitial fibrosis (RIF). Method: Cryopreserved umbilical cord mesenchymal stem cells were infused via tail vein injection into rats with unilateral ureteral obstruction and Sham-operated. Blood, kidney, heart, liver, spleen and lung were collected at 14, 21, and 28 days after infusion. Testing included microscopic observation of kidney morphological changes and immunohistochemical testing to identify and count the number of MAB1281 (labeled human cells) positive cells in the heart, liver, spleen, lungs, and kidneys of different treatment groups. Results: There was no significant difference in the Sham-operated group and Sham-operated + cell transplantation group at different time points. Human cells were identified mainly in the lungs, spleen, and kidney. The number of human umbilical cord mesenchymal stem cells in the kidney was greater in the unilateral ureteral obstruction + cell transplantation group, compared to the Sham-operated + cell transplantation group. human umbilical cord mesenchymal stem cells were mainly located in the interstitium of the left kidney. These results suggest that infused mesenchymal stem cells were primed to engraft a damaged kidney, especially damaged renal interstitium. Conclusions: Intravenous infusion of exogenous umbilical cord mesenchymal stem cells is feasible and safe. Infused mesenchymal stem cells can reach damaged kidney tissues with obstructive RIF after a vein graft.

Number and function of peripheral blood endothelial progenitor cells in Henoch-Schönlein purpura nephritis children with different degrees of renal vascular lesions

The aim of this study was to explore the correlation between different degrees of renal vascular lesions in children with Henoch-Schönlein purpura nephritis (HSPN) and changes in progenitor cell number and function in peripheral blood. Forty-eight HSPN patients were divided into three groups, mild, moderate and severe, according to the degree of renal vascular lesions. Peripheral blood mononuclear cells were isolated and cultured. Endothelial progenitor cells (EPCs) were identified by immunofluorescence assay. The number of EPCs and the migration and adhesion of EPCs were detected by flow cytometry. The numbers of peripheral blood CD34+, kinase insert domain receptor+ (KDR+) and CD133+ cells were lower in the severe and moderate vascular lesion groups compared with the mild vascular lesion group (all P<0.05) and were also lower in the severe vascular lesion group compared with the mild and moderate vascular lesion groups (all P<0.05). The adhesion and migration of EPCs were reduced in turn in the mild, moderate and severe groups. There were significant differences between the severe group and the mild and moderate groups (all P<0.05). Renal vascular lesions are involved in the occurrence and development of HSPN, while the number of EPCs, migration and adhesion of EPCs are important factors in renal vascular lesions.

Podocalyxin expression in renal tissues and correlation with the number of urinary podocytes in children with Henoch-Schonlein purpura nephritis.

OBJECTIVE To analyze the podocalyxin (PCX) expression in the kidney and the number of urinary podocytes in different pathological grades of Henoch-Schonlein purpura nephritis (HSPN), and to determine whether the number of urinary podocytes reflects the renal damage in HSPN. METHODS Fifty-six children diagnosed with HSPN in our hospital were enrolled in the study and classified into 4 groups by renal pathology: grade II (IIa+IIb) (n=10), grade III (IIIa+IIIb) (n=21), grade IV (n=16), and grade V (n=9). Four kidney autopsy specimens without histomorphologic lesions and 8 urine samples from healthy children served as controls. With immunofluorescence assay, the PCX expression in 4 normal renal tissues and in the renal tissues of the 56 HSPN children was detected and quantitatively analyzed. Positive rate and the number of urinary podocytes were detected in the 8 healthy children and 56 HSPN children. RESULTS In the renal tissues of the normal control group and grade II (IIa+IIb) HSPN group, the PCX expression was complete. The percentage of the PCX positive area out of the total glomerular area in the renal tissues of 2 groups had no significant difference (P>0.05). In the renal tissues of grade III (IIIa+IIIb), IV, and V HSPN groups, the PCX expression showed various degrees of loss, decreasing in turn from grade II (IIa+IIb), III (IIIa+IIIb), IV to V, with significant differences between each group (P<0.01). For HSPN with grade III (IIIa+IIIb) or higher, positive PCX expression was found in the urine, suggesting the presence of enough podocytes in the urine. The percentage of fluorescence positive area out of the total glomerular area of PCX in the renal tissues was negatively correlated with the total number of urinary podocytes (r=-0.637, P<0.01). CONCLUSION Podocyte injury plays a certain role in the pathological progression of HSPN. The urinary detection of podocytes can reflect the degrees of pathological damage in HSPN.

Sympathetic nervous system level and ambulatory blood pressure in children with primary nephrotic syndrome

OBJECTIVE To explore the change in ambulatory blood pressure monitoring (ABPM) value and the sympathetic nervous system (SNS) level in children with primary nephrotic syndrome(PNS) and their relationship. METHODS ABPM and casual blood pressure(CBP) were tested in 114 children with PNS and 12 normal children as a control group. The 24-h urine noradrenaline(NA), adrenaline(A) and dopamine(DA) content were detected through high-performance liquid chromatography with electrochemical luminescence and the correlation with ABP was analyzed. RESULTS Among 114 children with PNS, 101 had elevated blood pressure (88.6%), 45 showed high incidence of masked hypertension (39.5%), and 80 non-dipper blood pressure (70.2%). Systolic blood pressure level and blood pressure load were greater than diastolic blood pressure. NA, A, and DA levels of the PNS group were significantly higher than those of the control group, while those of the elevated blood pressure group were significantly higher than those of the normal blood pressure group in PNS children. SNS levels were positively correlated with blood pressure levels and blood pressure load, and negatively correlated with night BP decreasing rates. CONCLUSION Children with PNS have high incidence of hypertension with large proportion of masked hypertension and non-dipper blood pressure. Severe masked hypertension classification should be set up. In PNS children, SNS activity is elevated that might evaluate the blood pressure level and decrease blood pressure circadian rhythm.