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Objective To study the correlation between the diffusion-weighted imaging (DWI) measurements and glomerular filtration rate (GFR), Katafuchi scores in IgA nephropathy. Methods Thirty-five patients with IgA nephropathy (IgAN group) and twenty healthy volunteers (control group) were enrolled in this study. All of the subjects underwent bilateral renal DWI measurements with 3.0T MRI scanner. The values of apparent diffusion coefficient (ADC) of renal cortex and medulla were measured. GFR of IgAN group was detected with 99Tcm-DTPA scintigraphy. Based on the Lee classification and the Katafuchi score system, the pathological grading was carried out in patients of IgAN group. The ADC values were compared between control group and different grades of IgAN group. The correlations between ADC and GFR values were analysed in defferent groups. The correlations between ADC values and Katafuchi scores were analysed in IgAN group. Results The renal cortical ADC values were significantly higher than medulla ADC values in both control group and IgAN group (P 0.05). There was a positive correlation between the renal cortical and medulla ADC values and the GFR values in IgAN group (P medulla ADC values and the Katafuchi scores in IgAN group (P<0.05). Conclusion The diffusion-weighted imaging can reflect the physiological functions of kidney. It was feasible for application DWI in IgA nephropathy, which can be used for assessing the renal filtration function and the pathological damage. However, DWI measurement is not sensitive to early renal disease.
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Objective To study the effects of erythropoietin (rhEPO) in high glucose induced proliferation and apopto?sis of human kidney proximal tubular epithelial (HK-2) cells, and the possible mechanism thereof. Methods HK-2 cells cultured in vitro were divided into several groups randomly:blank control group, high glucose group, mannitol group, rhEPO control group, different concentrations of rhEPO treatment groups (5, 10, 20 U/mL) and Rho kinase group. The reverse tran?scription polymerase chain reaction (RT-PCR) was used to evaluate the mRNA levels of RhoA and ROCK after 24 hours. Tetrazolium salt method (MTT) was used to determine the cell proliferation. Cell apoptosis was detected by flow cytometry. Results Compared with blank control group the expression levels of RhoA and ROCK1 mRNA were significantly in?creased in high glucose group (P < 0.05). RhoA, ROCK1 mRNA expressions significantly decreased in rhEPO group than those of high glucose group (P<0.05). There was a positive correlation between the expression levels of RhoA mRNA and ROCK1 mRNA in high glucose group and rhEPO group. MTT method showed that rhEPO significantly promoted the prolifer?ation of HK-2 cells (P<0.05). Flow cytometry analysis showed that high glucose induced apoptosis in HK-2 cells, which was significantly inhibited in rhEPO group and Rho kinase group as compared to that of high glucose group in a concentra?tion dependent manner (P<0.05). Conclusion rhEPO can promote HK-2 cell proliferation and inhibit apoptosis, which may be related to RhoA/ROCK signaling pathway.
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Objective Clinical treatment can delay the development of renal interstitial fibrosis , but it can not reverse renal dysfuntion.The article was to discuss the influence of recombinant human erythropoietin ( rHuEPO ) on inflammatory factors in the process of renal interstitial fibrosis and its possible mechanism . Methods The vitro cultured HK-2 cells were randomized into 7 groups:the blank control group , rHuEPO control group ( addition of 20U/mL rHuEPO), albumin stimulation group (addition of 5mg/mL albumin), 5mg/mL rHuEPO intervention group (5mg/mL albumin +5U/mL rHuEPO), 10 U/mL rHuEPO intervention group (5mg/mL albumin +10 U/mL rHuEPO), 20U/mL rHuEPO intervention group (5mg/mL albumin +20U/mL rHuEPO), and Rho inhibi-taion group (addition of 5mg/mL albumin 30min after 10μmol/L Y27632), 24 h acting time for each group.We observed the changes of cell morphology in each group .Reverse transcription polymerase chain reaction ( RT-PCR) was used to evaluate the mRNA levels of RhoA, ROCK1 and IL-6 , and ELISA was applied to measure the levels of supernatant TNF-αand IL-6 protein. Results The form of pebbles or paving stone was observed in blank control group and rHuEPO intervention groups , a long and thin spindle change with the appearance of fibre cells in albumin stimulation group , the transformation to pebbles in 5, 10, 20 mg/mL rHuEPO intervention groups , the form of oval and slightly increased intercellular space in Rho inhibitaion group .Compared with the blank control group , the expressions of RhoA mRNA, ROCK1 mRNA and IL-6 mRNA significantly increased in the albumin stimulation group (P<0.05), while significantly reduced in 5, 10, 20 mg/mL rHuEPO intervention groups (P<0.05), which was in negative relation with the rHuEPO concentrations .Compared with the albumin stimulation group , the expressions of ROCK 1 mRNA and IL-6 mRNA reduced in Rho inhibtation group (P<0.05), while there was no significant difference as to the expression of RhoA mRNA .ELISA results showed:compared with blank control group , the expressions of supernatant TNF-α([452.32 ±33.23] ng/L vs [1347.54 ±41.52] ng/L), IL-6 protein([884.62 ±0.73] pg/L vs [95.12 ±0.32]pg/LP<0.05) increased significantly.Compared with albumin stim-ulation group, the expressions of TNF-αin 5, 10, 20 mg/mL rHuEPO intervention groups and Rho inhibitation group reduced signifi-cantly([1003.32 ±3.42] ng/L, [821.32 ±21.32] ng/L, [590.15 ±7.68] ng/L, [488.13 ±65.03] ng/L vs [1 347.54 ± 41.52]ng/L,P<0.05), while the expressions of IL-6 mRNA reduced accordingly in 5, 10, 20 mg/mL rHuEPO intervention groups and Rho inhibitation group reduced significantly ([656.68 ±0.55] pg/L, [422.35 ±0.22] pg/L, [217.32 ±0.35] pg/L, [309.49 ±0.21] pg/L vs [884.62 ±0.73]pg/L,P<0.05).Moreover, there was significant statistical difference among 5, 10, 20 mg/mL rHuEPO intervention groups(P<0.05). Conclusion RHuEPO can inhibit the transdifferentiation process of HK-2 cells in-duced by albumin by suppressing inflammation factors , and the mechanism may be involved in RhoA/ROCK signaling pathway .
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The effect of retinoic acid (RA) on renal interstitial fibrosis (RIF) is important. Notch signaling is known to play an important role in the pathological injury of RIF. This study summarized recent research progress of the effect of RA on RIF and Notch signaling. Interruption of Notch signaling by RA might be a potential anti-fibrotic strategy in RIF.
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Objective The core mechanism of renal insterstitial fibrosis (RIF) is epithelial-mesenchymal transition.This study aimed to investigate the effect of erythropoietin on high glucose-induced epithelial-mesenchymal transition ( EMT) of normal hu-man kidney proximal tubular epithelial cells (HK-2) and its possible mechanism. Mothods HK-2 cells cultured in vitro were ran-domly divided into a blank control group , a high glucose induction group , a mannitol induction group , an EPO induction group , an EPO (5, 10, and 20U/mL) inhibition group, and an Rho kinase inhibitor group.After 24 hours of intervention, the mRNA levels of RhoA and ROCK were determined by RT-PCR, those of E-cadherin and α-smooth muscle actin (α-SMA) proteins detected by immu-nofluorescence staining , and the expression of FN proteins in the supernatant measured by ELISA . Results Compared with the blank control group , the expressions of RhoA and ROCK 1 mRNA were significantly increased in the high glucose induction group (0.945 ±0.132 vs 1.400 ±0.022, 1.007 ±0.002 vs 1.913 ±0.011, P<0.05), but markedly decreased in the 5, 10, and 20U/mL EPO inhibition groups (1.400 ±0.022 vs 1.278 ±0.006, 1.400 ±0.022 vs 0.770 ±0.005, 1.400 ±0.022 vs 0.334 ±0.009, P<0.006) in comparison with the high glucose induction group , and the effects were related to the concentration of EPO .Compared with the blank control, the expression of E-cadherin protein was increased in the high glucose induction group (0.644 ±0.006 vs 0.107 ± 0.004, P<0.05), but remarkably decreased in the 5, 10, and 20 U/mL EPO inhibition groups (0.236 ±0.006, 0.433 ±0.010, 0.521 ±0.010) in comparison with the high glucose induction group (P<0.05), and the effects were also related to the concentration of EPO.Pearson correlation analysis showed a positive correlation between the mRNA expressions of RhoA and ROCK 1 in the high glu-cose induction and EPO inhibition groups . Conclusion EPO can inhibit high glucose-induced epithelial-mesenchymal transition of normal human kidney HK-2 cells and thus delay renal fibrosis , which mignt be related to the RhoA/ROCK signaling pathway .
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In recent years , active vitamin D is a hot research drugs because of its renal protective effect of independent regu -lation of anti-inflammatory effects outside calcium and phosphorus metabolism , regulation of apoptosis , mediated immunity and reduc-tion of proteinuria .Podocyte is the main target of active vitamin D based on the result of clinical and animal studies .In this article, we review the current literature on mechanism of active vitamin D and its analogues on the protection of podocytes about and give the clini -cal perspectives of activity vitamin D .