ABSTRACT
To explore a new approach for the treatment of renal interstitial fibrosis (RIF), we detected the expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF). Twenty-four male Sprague Dawley (SD) rats were randomly divided into 2-week normal control (2NC) group, 4-week NC (4NC) group, 2- week unilateral ureteral obstruction (2UUO) group, and 4-week UUO (4UUO) group. We performed left ureteral ligation on UUO groups. Then, we sacrificed the rats of the 2NC group and 2UUO group at 2 weeks and the other groups at 4 weeks after the surgery. Immunohistochemistry and western blot were applied to detect the expression of MMP9, VEGF, fibronectin (FN), type IV collagen (Col-IV), and transforming growth factor-ß1 (TGF-ß1). MMP9 levels reduced after UUO surgery. Its expression was less in the 4UUO group than in the 2UUO group (P<0.05). The expression of VEGF, TGF- ß1, FN, and Col-IV was higher in UUO groups than in NC groups (P<0.05). The expression of these indicators was higher in the 4UUO group than in the 2UUO group (P<0.05). In the correlation analysis, MMP9 levels in UUO groups had a negative correlation with the expression of TGF-ß1, VEGF, Col-IV, FN, and RIF index (all P<0.05). In UUO groups, VEGF levels had a positive correlation with the expression of TGF-ß1, Col-IV, FN, and RIF index (all P<0.05). In conclusion, with the aggravation of RIF lesions, MMP9 levels decreased, and VEGF levels increased. Whether there is a mutual inhibition relationship between them remains to be confirmed by further experiments.
ABSTRACT
BACKGROUND: Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia. METHODS: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-ß1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 µM DFO, and 25 µM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 µM DFO were added, and cells were cultured for another 24 hours before analysis. RESULTS: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 µM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-ß1, HIF-1α and NCoA-1. CONCLUSION: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.
ABSTRACT
Introduction: Patients with steroid-dependent nephrotic syndrome (SDNS) suffer frequent relapse with adverse effects caused by long-term prednisolone treatment. Recently, the chimeric monoclonal antibody against the protein CD20 (rituximab - RTX) was observed to be efficacious and safe in the treatment of patients with SDNS. We summarized the scientific literature to evaluate RTX therapy in the clinical management of SDNS. Material and methods: PubMed, EMBASE, and Cochrane Library databases were investigated from interception to 2019-6-6, without language limitation. The analysis was restricted to adults ≥ 19 years of age. Data were administered and analyzed through the Review manager 5.3 software. Results: After RTX treatment, relapse times, prednisolone dose, and proteinuria decreased, whereas serum albumin was increased. The clinical parameters blood pressure and total cholesterol diminished also, whereas bone mineral density was improved. Overall, RTX ameliorated the adverse effects of prednisolone. Moreover, the Th1/Th2 ratio was changed except for the CD19 and CD20 cell counts. Additionally, most of the adverse effects of RTX were mild and well tolerated. Conclusions: In the studies that we considered, we concluded that RTX treatment was effective and safe in the therapy of patients with SDNS. Nevertheless, more randomized controlled trials are required to explore the mechanism of RTX action and verify its efficacy.
ABSTRACT
Vascular endothelial growth factor (VEGF) is a heparin-specific growth factor specific for vascular endothelial cells and induces angiogenesis via binding to vascular endothelial growth factor receptor (VEGFR). Chronic kidney disease (CKD), accompanied by microvascular disease, is recognized as an irreversible reduction of renal function. The effects of VEGF on CKD risk were evaluated in this study. 121 CKD patients and 50 healthy volunteers were evaluated in the current study. Data mining using the China Biological Medicine (CBM) and NCBI/PubMed databases, was performed and applicable investigations were pursued. Pooled mean differences (MD) and pooled odds ratios (OR), with corresponding confidence intervals (CIs), were calculated by meta-analysis. The levels of Scr, BUN and VEGF in the CKD group were significantly higher, when compared with the control group (P < 0.01). For the meta-analysis, thirteen articles and our current study were evaluated. VEGF levels was found to be associated with CKD risk (P < 0.00001). In the sub-group meta-analysis, we found that the pooled MD of VEGF levels was related to the early CKD group, although the difference was not notable. However, the meta-analysis itself indicated that the pooled MD of VEGF levels were in accordance with severe CKD group (P < 0.00001). Furthermore, VEGF +936C/T T allele was not associated with CKD risk (P = 0.69). VEGF levels are apparently associated with CKD risk, especially in more severe CKD. Gene polymorphism analysis indicates that the VEGF +936C/T T allele is not associated with CKD risk.
