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【Objective】 To investigate the effects of chlorogenic acid on the proliferation, migration and invasion of renal carcinoma A498 and 769-P cells and the possible molecular mechanism. 【Methods】 Human renal carcinoma A498 and 769-P cells were divided into control group and chlorogenic acid group (2 μL,1 μmol/L) and cultured for 72 h. The cell proliferation, invasion and migration were detected with MTT assay, Transwell assay and scratch test, respectively. The expressions of IL-1β, EPAS-1 and AKT/P65 signaling pathway related proteins were detected with ELISA, qRT-PCR and Western blot, respectively. 【Results】 Chlorogenic acid inhibited the proliferation, invasion and migration of renal carcinoma A498 and 769-P cells, and reduced the IL-1β level in the cell supernatant. Anti-IL-1β reduced the protein and mRNA expressions of EPAS-1, p-AKT and p-P65. Compared with the control group, the chlorogenic acid group had reduced mRNA and protein expressions of EPAS-1, p-AKT and p-P65 (P<0.05). 【Conclusion】 Chlorogenic acid can inhibit the invasion and metastasis of renal carcinoma cells, and its mechanism may be related to inhibiting the secretion of IL-1β, thereby inhibiting the AKT/P65/EPAS-1 pathway.
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Abstract Objective: To explore possible genes related to the development of persistent pulmonary hypertension of the newborn (PPHN). Methods: The authors identified 285 single nucleotide polymorphisms (SNPs) of 11 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, NOTCH3, SOD3, CPS1, ABCA3, ACVRL1, and SMAD9), using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. The FastLmmC and R package was used for statistical analyses. The chi-square test and Cochrane-Armitage trend test were used to compare the allele and genotype frequencies between the groups and to test the genetic models, respectively. Results: A total of 45 PPHN infants and 294 control subjects were analyzed. The most common cause of PPHN was meconium aspiration syndrome. Among the 285 SNPs, 17 SNPs from 6 candidate genes (BMPR2, EPAS1, PDE3A, VEGFA, ENG, and NOTCH3) were significantly associated with PPHN (P < 0.05). After using the Bonferroni correction (P < 0.00018), only the rs17034984 SNP located in intron 1 of the EPAS1 gene remained significantly different between the PPHN and control subjects (P = 0.00014). The frequency of the TC/TT genotype of rs17034984 in the gene with the dominant model was significant in the patients with PPHN (OR = 5.38, 95% CI: 2.15-13.49). The T allele frequency of rs17034984 in the gene showed a significant difference compared with the control subjects (OR = 4.89, 95% CI: 2.03-11.82). Conclusions: The present study suggests that the rs17034984 variant of EPAS1 gene is associated with PPHN.
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Objective This study explored whether EPAS1 gene is involved in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) during hypoxia when EPAS1 gene expression was interfered by small interfering RNA (siRNA).Methods The rat primary pulmonary artery smooth muscle cells were cultured and identified by immunofluorescence.The specific lipidosomes of EPAS1 siRNA were constructed and transfected into PASMCs,and the best targets were selected from the three interfering targets.The transfected PASMCs were cultured in hypoxia (37℃,5％ CO2,2％ O2) or normoxia (37℃,5％ CO2,20％ O2) for 24h,48h and 72h,respectively.The PASMCs proliferation was detected by CCK-8 assay.The protein expression of EPAS 1 and vascular endothelial growth factor (VEGF) were determined by Western blotting to investigate the effect of silencing EPAS1 gene expression on the proliferation of PASMCs under hypoxic condition.Results The specific liposomes ofEPAS1 siRNA were successfully constructed and transfected into PASMCs,and the best interfering target were selected from the three interference targets.The proliferation of PASMCs was increased and the protein expression of VEGF was up-regulated in the PASMCs under hypoxic condition.Under hypoxic or normoxic condition,PASMCs proliferation and VEGF protein expression of PASMCs were suppressed by EPAS 1 siRNA.Conclusion EPAS 1 gene might be involved in the proliferation of rat PASMCs by regulating VEGF protein level under hypoxic condition.
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The indigenous populations of high altitude, physiologically with lower concentration of hemoglobin and higher level of nitric oxide, can be well-adapted to hypoxia and cold environment. Recent studies have revealed that these adaptive highland population possessed genetic bases, which involved a number of genes, such as EPAS1, EGLN1, CBARA1, VAV3, PPARA, and eNOS, associating with hypoxia-inducible pathway, production of red blood cells and vasodilator substances, etc. These findings provided new insights and strategies from genetics to uncover the unique natural environment selection, to understand the mechanisms of plateau diseases, finally to better prevent and treat them.
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Lung cancer is feared to be deadly and is caused due to the involvement of a cascade of proteins significant among which are EPAS1, Thrombomodulin, Metallothionein and Matrix Metallo Proteinase. The evolutionary aspects of these proteins are important to study the extent of conservation and mutation across different generations in diverse species. The rooted and unrooted tree would depict the relatedness among organisms and the ancestor of the organisms involved in the study. The evolutionary histories of groups of species are one of the most widely used tools throughout the life sciences, as well as objects of research with in systematic, evolutionary biology. In every phylogenetic analysis reconstruction produces trees. These trees represent the evolutionary histories of many groups of organisms, bacteria due to horizontal gene transfer and plants due to process of hybridization. Through comparison with several species of healthy organism, one may determine where the defective mutation is located, and then determine how to treat the disease. This strategy may help us to identify the mutations that had occurred in evolutionary conserved residues. We feel this method can be useful for understanding evolutionary rate variation, and for understanding selection variation on different characters. The various tree topologies along with their significant homolog’s would enable a thorough understanding of the disease.
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Objective To evaluate the expression of endothelial Per-ARNT-Sim domain protein-1(EPAS-1)/hypoxia-inducible factor-2?(HIF-2?) and its relationship with vascular endothelial growth factor (VEGF) in bladder transitional cell carcinoma (BTCC). Methods The expression of EPAS-1/HIF-2? and VEGF by immunohistochemical staining was examined in 60 cases of BTCC (Grade Ⅰ in 28 cases,Grade Ⅱ in 12,Grade Ⅲ in 20) and 8 subjects with normal urothelium. Of the 60 cases 29 had superficial (≤pT 1) bladder cancer and 31 had invasive (≥pT 2 bladder cancer).?2 test was used to assess the relationship between EPAS-1/HIF-2? and VEGF expression versus tumor grade and stage. Results The expressions of EPAS-1/HIF-2? and VEGF were negative in all normal bladder tissue but high in BTCC.Of the 60 cases,34 (56.6%) were positive and 26 ( 43.4%) were negative for EPAS1/HIF-2?.Four cases (14.3%) of Grade Ⅰ,11 (91.7%) of Grade Ⅱ and 19 (95.0%) of Grade Ⅲ were positive for EPAS-1/HIF-2?. Positive staining was seen in 5 (17.2%) of the superficial and 29 (93.5%) of the invasive cancer cases.EPAS-1/HIF-2? positivity was correlated with high histological grade (r=0.862,P