Vascular calcification (VC) plays as a critical role on cardiovascular disease (CVD) and acts as a notable risk factor in cardiovascular system. Vascular smooth muscle cells (VSMCs) calcification can be triggered by high phosphate treatment; however, the explicit mechanism remains unclear. In the present study, we isolated VSMCs from primary rat artery, applied β‐GP (β‐glycerophosphate) for inducing VSMCs calcification in vitro to explore the mechanism of phosphate‐induced calcification in VSMCs. Alizarin red staining was performed to assess the mineralization in VSMCs. Calcium deposition experiment was taken to evaluate the calcium content. ALP staining was determined to assess the ALP activity. The recombinant adenoviruses were constructed for the overexpression of Klotho and FGF23, respectively. qRT‐PCR and western blot analysis were subjected to measure the expression of Klotho/FGF23 and correlated genes among Wnt7b/β‐catenin pathway. We found that the calcium content was obviously increased and Alizarin red staining was positive in calcification group exposure with high phosphate in a time‐dependent manner. The expression of Klotho and FGF23 was significantly decreased in the calcification group. However, overexpression of Klotho and FGF23 markedly reversed VSMCs calcification stimulating with high phosphate treatment. Moreover, Wnt7b/β‐catenin inhibitor DKK1 could partly attenuate the effect of high phosphate on calcified VSMCs. These findings demonstrated that Klotho/FGF23 axis could modulate high phosphate‐induced VSMCs calcification via Wnt7b/β‐catenin signaling pathway. Our findings unravel that Klotho/FGF23‐ Wnt7b/β‐catenin axis functions as a crucial role in the VSMCs calcification.
Objective: This study aims to investigate the clinical value of serum Klotho and FGF23 in cardiac valve calcification in patients with chronic kidney disease (CKD). Methods: In the present study, 180 patients with CKD, who were admitted to the department of nephrology of our hospital on April 1, 2016 (solstice, 2019), were selected as the main subjects. According to the CKD stage, these patients were divided into three groups: CKD2~3 group, CKD4 group, and CKD5 group. In each group, ultrasound was used to evaluate the cardiac valve calcification, and the independent risk factors for cardiac valve calcification were analyzed by Logistic regression. Results: The levels of hemoglobin and blood calcium in CKD2~3 patients were higher than those in CKD4 and CKD5 patients, and the levels of hemoglobin and blood calcium in CKD5 patients were higher than those in CKD4 patients (P<0.05). Albumin was lower in CKD2~3 patients when compared to CKD5 patients while albumin was higher in CKD5 patients when compared to CKD4 patients (P<0.05). The serum levels of FGF23 was lower in CKD2~3 patients when compared to CKD4 and CKD5 patients while the serum levels of FGF23 was lower in CKD4 patients when compared to CKD5 patients (P<0.05). The serum levels of Klotho was higher in CKD2~3 patients, when compared to CKD4 and CKD5 patients, while the serum levels of Klotho was higher in CKD4 patients, when compared to CKD5 patients (P<0.05). The logistic regression analysis revealed that GFR, serum creatinine, FGF23 and Klotho were independent risk factors for cardiac valve calcification in patients with CKD. Conclusion: With the decrease of GFR in CKD patients, the serum levels of FGF23 increases, while the serum levels of Klotho decreases. Furthermore, the serum levels of FGF23 and Klotho are affected by various factors, and the levels of FGF23 and Klotho in CKD patients are negatively correlated. GFR, serum creatinine, FGF23 and Klotho are independent risk factors for heart valve calcification in patients with CKD.
In order to compare the effects of iopromide and isoxazole on postoperative contrast-induced nephropathy in patients with renal insufficiency, the paper searches for randomized controlled trials and retrospective cohort studies comparing the effects of iopromide and iodixanol on renal function in patients with renal insufficiency after surgery. The data are extracted from eligible studies. We tried to assess the incidence of contrast-agent nephropathy, preoperative and postoperative serum creatinine indicators, and mortality. This paper includes 8 studies with a total of 1243 patients. The incidence of contrast-induced nephropathy in the iopromide group is higher than that in the iodixanol group, and there is no significant difference between the two groups in postoperative mortality and preoperative serum creatinine expression. Sensitivity analysis and funnel chart show that our research is robust and has low publication bias. Our research shows that in patients with renal insufficiency, the incidence of contrast-medium nephropathy in the iopromide group is higher than that in the iodixanol group. Iodixanol is safer and has less effect on patients’ serum creatinine levels.
Background The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood. Methods In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein–protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM). Results We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo , we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM. Conclusion VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-022-02936-y.
Backround: PLA2R-associated IMN covers 70% of IMN, which is one of the main types of chronic kidney disease in adults and one of the most common causes of end‑stage renal disease. Vascular endothelial growth factor A (VEGFA), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis, which lead to numerous kidney diseases, including TSHD7A-associated IMN. However, the role of VEGFA in PLA2R-associated IMN is still poorly understood.Methods: We downloaded the microarray data GSE115857 from GEO. The DEGs were identified with R software, and the functional and pathway enrichment analysis of DEGs was performed utilizing the DAVID and Cytoscape ClueGo plug-in. A comprehensive list of interacting DEGs was constructed using the STRING database and visualized by Cytoscape software. The Cytoscape MCODE and cytoHubba plug-in were used to identify clustered sub-networks, and hub genes from the protein-protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signaling pathway in IMN. Results: There were 1422 genes (952 up-regulated genes and 470 down-regulated genes) were identified as DEGs in GSE115857. The BP of DEGs in GSE115857 was clustered in regulation of transcription from RNA polymerase II promoter, positive regulation of nuclear-transcribed mRNA poly(A) tail shortening, cell adhesion et al. The KEGG pathway of DEGs in GSE115857 was clustered in Rheumatoid arthritis, ABC transporters, PI3K/AKT signaling pathway et al. Then we got a huge PPI network from STRING. 6 modules were screen out to study the functional changes in IMN. The KEGG pathway of module 3 was enriched in soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) interactions in vesicular transport. There were 3 hub genes screened out, namely, VEGFA, JUN,and FOS. Following the random walk, all genes were ranked and GSEA analysis showed that the signaling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. CONCLUSION: In summary, this study reveals VEGFA promotes PLA2R-associated IMN by stimulating angiogenesis via PI3K/AKT signaling. Moreover, SNARE interactions in vesicular transport was involved in the development of PLA2R-associated IMN, which may offer a novel therapeutic strategy in treatment of IMN.
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