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Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.
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Objective:To assess the value of urine heat-shock protein-70 (HSP-70) in the early diagnosis of acute kidney injury (AKI) after cardiac cardiopulmonary bypass (CPB).Methods:Patients with cardiopulmonary bypass from May 2018 to July 2018 in Henan Provincial People's Hospital were enrolled as subjects. Urine samples were collected before and after cardiopulmonary bypass at 0 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h. Patients were divided into AKI group and non-AKI group according to the Kidney Disease: Improving Global Outcomes Guide. Urinary HSP-70, tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected by enzyme-linked immunosorbent assay (ELISA) and urine neutrophil gelatinase-associated lipocalin (NGAL) was determined by immunoturbidimetry. The receiver operating characteristic (ROC) curve was plotted to calculate the critical value, sensitivity and specificity of urine HSP-70, [TIMP-2]×[IGFBP7] and NGAL for the diagnosis of postoperative AKI after CPB.Results:A total of 45 patients were enrolled in the study. There were 24 cases in AKI group and 21 cases in non-AKI group. The level of urinary HSP-70, [TIMP-2]×[IGFBP7] and NGAL in AKI group were significantly higher than in the non-AKI group at each postoperative time point, with statistically significant differences (all P<0.05). The level of urinary HSP-70 in AKI group peaked at 2 h after CPB, which was significantly earlier than the peak time of urine [TIMP-2]×[IGFBP7] and urine NGAL (12 h after CBP and 4 h after CBP, respectively). Urinary HSP-70≥2.1 μg/L could predict postoperative AKI of CPB at 2 h after CPB, with the area under the curve ( AUC) of 1.00, the sensitivity of 100.0% and the specificity of 100.0%. Urinary [TIMP-2]×[IGFBP7]>19.1 μg 2/L 2 could predict postoperative AKI of CPB at 12 h after CPB with the AUC of 0.94, the sensitivity of 87.5%, and the specificity of 100.0%. Urinary NGAL>27.4 μg/L could predict postoperative AKI of CPB at 4 h after CPB with the AUC of 0.95, the sensitivity of 95.8%, and the specificity of 85.7%. The positive predictive value of urine HSP-70≥2.1 μg/L at 2 h after CPB was 100.0%, and the negative predictive value was 100.0%. Conclusions:The level of urinary HSP-70 increases earlier than that of urinary [TIMP-2]×[IGFBP7] and NGAL in patients with AKI after CPB. Clinical monitoring of urinary HSP-70 level contributes to early diagnosis of AKI.
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Objective To explore the condition of cortistatin (CST)expression in human renal tissue and the changes in the level of CST in IgA nephropathy (IgAN)of different degrees.Methods Ten tumor adjacent normal renal tissue samples were collected.The mRNA and protein expressions of CST in human renal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR)and Western blotting,respectively.Immunohistochemisty (IHC)was performed to locate the expression of CST in renal tissue.According to the grading system of Lee et al,IgAN was divided into three groups:grade Ⅰ -Ⅱ (group A),grade Ⅲ -Ⅳ (group B),and grade Ⅴ (group C),and ten renal biopsy tissue samples were collected for each group.IHC was performed to detect the change in the level of CST in normal and IgAN renal tissue of different degrees.The effect of clinical indices on the level of CST in IgAN renal tissue was assessed by multiple linear regression analysis.Results RT-PCR and Western blotting showed that CST was expressed in renal tissue and IHC showed that CST was expressed on renal tubular epithelial cells.In IgAN,the higher the pathological grade was, the higher the expression of CST in renal tubules was.Multiple linear regression analysis showed that the pathological grade was associated with the expression of CST in renal tissue (r =0.875,P <0.01).Conclusion CST may participate in the inflammatory reaction of IgAN pathological injury and exert anti-inflammation effects.