Systemic lupus erythematosus is an autoimmune disease involving multiple organs of the body. Lupus nephritis is one of the most serious organ manifestations of systemic lupus erythematosus. Vimentin, a member of the intermediate filament protein family, is involved in the pathogenesis of many autoimmune diseases, including lupus nephritis. More and more studies have shown that vimentin plays an important role in the pathogenesis of lupus nephritis, and has an important influence on the disease development, treatment and prognosis of lupus nephritis. This review focuses on the structure, function and post-translational modification of vimentin, the relationship between vimentin and the pathogenesis of lupus nephritis, and the significance of vimentin expression levels in renal tissues, serum and urine, in order to provide theoretical basis for future mechanism research and clinical application.
ObjectiveTo explore the effectiveness of Ovol2 gene for epithelial-mesenchymal transition (EMT) to offer some theory evidences for the targeted therapy in lung adenocarcinoma. MethodsA549 cells were treated with control and Ovol2 overexpressioned by lentivirus infection. Real-time PCR were performed to test the mRNA level of genes correlated to EMT. Western Blot was performed for protein level of the following makers:E-cadherin, N-cadherin, vimentin, ect. Moreover, we tested the migration and invasion ability of A549 cells by transwell and wound healing experiment. ResultsAfter treated with Ovol2 overexpressed, the expression level of E-cadherin raised, while the expression level of N-cadherin, vimentin and Twist1 declined in both mRNA and protein expression level. The results of wound healing and transwell experiment indicated that the migration and invasion ability of A549 cells weakened. ConclusionOverexpression of Ovol2 gene can suppress the distant metastasis ability and invasion ability of A549 cells by inhibiting the EMT.
ObjectiveTo investigate the role of GOLPH3 in esophageal squamous cell carcinoma (ESCC). MethodsWound healing assays, transwell invasion assays and 3D culture were carried out to analyze the cell migration and invasion ability of GOLPH3 overexpression and knockdown KYSE-140 cells. The relationship between GOLPH3 expression and CYR61, CD44 and Snail mRNA expression was further examined through qRT-PCR, to identify the mechanisms involved. ResultsGOLPH3-promoted ESCC cell migration and invasion. CYR61, CD44 and Snail mRNA expression levels were correlated with GOLPH3 protein expression level. ConclusionGOLPH3 overexpression promotes ESCC metastasis through epithelial-mesenchymal transition (EMT), and plays an oncogenesis role in ESCC.
Objective To investigate the structure characteristics， functions， and research progress of Notch signaling pathway in digestive tumors. Methods The related literatures about the molecular genetic mechanism of Notch signaling pathway were reviewed. Results The Notch signaling pathway plays an important role not only in normal cells’ growth， differentiation， proliferation， and apoptosis but also in a variety of tumors’ occurrence and development. Conclusion The reasonable regulation to Notch signaling pathway may open up new ways to the treatment of the tumor.
ObjectiveTo explore the role of interleukin-6 (IL-6) in cervical cancer cell C-33A.MethodsThe cervical cancer cells C-33A were divided into the IL-6 group and the control group after culture. The IL-6 group were treated with 50 ng/mL of recombinant IL-6 protein, and the control group were without IL-6. Then cell viability and cell migration were detected by MTT assay and wound-healing assay, respectively. The mRNA and protein expressions of epithelial-cadherin (E-Cad), neural-cadherin (N-Cad), vimentin and transcription factors-snail1 (TFs-SNAIL1) were analyzed by real time quantitative polymerase chain reaction and Western blotting, respectively.ResultsCompared with the control group, in the IL-6 group the proliferation of cervical cancer cells C-33A was promoted (12 h: 0.388±0.025 vs. 0.597±0.057; 24 h: 0.547±0.021 vs. 0.798±0.036; 48 h: 0.745±0.056 vs. 1.296±0.122; 72 h: 1.074±0.053 vs. 1.805±0.113; P<0.05), and the relative migration ability of cervical cancer cell was promoted (12 h: 1.057±0.029vs. 1.200±0.045; 24 h: 1.189±0.036 vs. 1.428±0.181; 48 h: 1.273±0.059 vs. 1.569±0.143; 72 h: 1.409±0.047 vs. 1.623±0.170; P<0.05); meanwhile, compared with the control group, in the IL-6 group, the expression of E-Cad mRNA (1.012±0.098vs. 0.483±0.171, P<0.01) and E-Cad protein (1.032±0.015vs. 0.395±0.119; P<0.01) decreased, the expression of N-Cad mRNA (1.054±0.106vs. 1.465±0.230, P<0.01) and N-Cad protein (1.040±0.043vs. 1.605±0.128, P<0.01) increased, the expression of vimentin mRNA (1.050±0.083vs. 1.340±0.099, P<0.05) and vimentin protein (1.043±0.062vs. 1.430±0.077, P<0.05) increased, and the expression of TFs-SNAIL1 mRNA (1.058±0.176vs. 1.510±0.229, P<0.01) and Fs-SNAIL1 protein (1.022±0.015vs. 1.470±0.139, P<0.01) increased.ConclusionIL-6 may promote the proliferation, migration, and epithelial-mesenchymal transition of cervical cancer cell C-33A.
ObjectiveTo summarize the role of epithelial-mesenchymal-transition （EMT） in occurrence and development of gastrointestinal cancer. MethodsDomestic and international publications online involving EMT of gastrointestinal cancer in recent years were collected and reviewed. ResultsEMT was a highly conserved process that has been well characterised in embryogenesis. Studies had shown that the aberrant activation of EMT in adult epithelia could promote tumour metastasis by repressing cell adhesion molecules. E-cadherin， one of the epithelial cell markers, maybe involved in the process of the EMT, especially of the Ecadherin transcriptional repressors， these transcriptional repressors significantly increased in the gastrointestinal cancer. Further more， EMT might involve in the process of gastrointestinal cancer stem cells formation. ConclusionsEMT and it’s regulators play a very important role in gastrointestinal cancer， and may provide a newsight into the gastrointestinal cancer. It also can provide a novel clinical targets to treat the gastrointestinal cancer.
Objective To study the effect of mechanical stretch on the microenvironment of BEAS-2B on macrophage polarization and the role of polarized macrophages in the epithelial-mesenchymal transition (EMT) of BEAS-2B. Methods Using enzyme linked immunosorbent assay to detect the changes in the levels of cytokines such as interferon-γ, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-10 in the supernatant of lung epithelial cells cultured statically and mechanically stretched. The M0 macrophages (derived from THP-1) were stimulated by stretch/static conditioned medium of BEAS-2B. The surface markers of M1 (CD197) /M2 (CD206) macrophages were detected by flow cytometer. Stretch/static conditioned medium were used to stimulate the co-culture system of macrophages and BEAS-2B in the presence or absence of platelet-derived growth factor receptor inhibitor (PDGFRi), then the protein expression level of EMT makers was examined by Western blot. Results Exposure of BEAS-2B to mechanical stretch resulted in significantly higher production of the pro-M1/M2 polarized factor. The EMT of the co-culture system of M0 and BEAS-2B could be induced by stretch conditioned medium, epithelial marker cytokeratin (CK)-8 and E-cadherin were decreased, while mesenchymal marker α-smooth muscle actin, N-cadherin and vimentin were increased in stretch conditioned medium group. The expression of platelet-derived growth factor (PDGF) was significantly higher in stretch conditioned medium group. The PDGFRi can block the EMT in stretch conditioned medium group. Conclusions The lung epithelial cell supernatant induced by mechanical stretch can promote the polarization of macrophages to M1 and M2. Polarized macrophages promote EMT in human lung epithelial cells via PDGF, and blocking PDGF might attenuate the VILI-associated lung fibrosis.
ObjectiveTo systematically review the prognostic value of E-cadherin expression in stage I non-small cell lung cancer (NSCLC). MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015), CNKI, CBM and WanFang Data were searched to collect cohort studies about the prognostic value of E-cadherin expression in stage I NSCLC from inception to Jun. 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 9 cohort studies, involving 1028 patients were included. The results of meta-analysis showed that, the lower E-cadherin expression group had a lower overall survival rate than that of the higher E-cadherin expression group (HR=1.74, 95%CI 1.36 to 2.24, P＜0.00001). However, there was no significant difference between two groups in disease free survival (HR=2.08, 95%CI 0.8 to 5.40, P=0.13). Subgroup analysis showed that, the lower E-cadherin expression group had a worse overall survival when groups were divided by different cut-off values, E-cadherin location site or different nations (all value P＜0.05). ConclusionCurrent evidence shows that, reduced E-cadherin expression could predict poor prognostic outcome in patients with stage I NSCLC. Due to the limited quantity and quality of included studies, the above conclusions need to be verified by more high quality studies.
Objective To investigate the prognostic value of epithelial-mesenchymal transition （EMT） related proteins （Snail， E-cadherin， and N-cadherin） in gastric cancer and its relationship with tumor initiating cells （TICs） marker （CD133）. Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test. Results ① The protein expression levels of Snail， N-cadherin， and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer （Snail：0.599±0.114 versus 0.259±0.108， P=0.020；N-cadherin：0.754±0.154 versus 0.329±0.134， P=0.001；CD133：0.635±0.119 versus 0.485±0.116， P=0.029）， while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer （0.378±0.123 versus 0.752±0.156， P=0.003）.② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion， lymphatic vessel invasion，N3 lymph node metastasis， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph node metastasis， diameter less than 5 cm， andⅠ＋Ⅱ staging（P＜0.05）， while E-cadherin protein expression was lower than that in the patients without vascular invasion， lymphatic vessel invasion， N0-N2 lymph nodes metastasis， andⅠ＋Ⅱstaging （P＜0.05）. The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion， diameter more than 5 cm， and Ⅲ＋Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion， diameter less than 5 cm， andⅠ＋Ⅱ staging （P＜0.05）. ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression， respectively （rs=0.278， P=0.048；rs=0.406， P=0.003）， while E-cadherin protein expression was significantly negative correlated with CD133 protein expression （rs=-0.504， P=0.000）.④ The survival time in the patients with lower expressions of Snail， N-cadherin， and CD133 were significantly longer than those in the patients with higher expressions of Snail， N-cadherin， and CD133 （P＜0.05）. The combination of Snail， N-cadherin， E-cadherin， and CD133 could effectively predict survival. Conclusions There is a significant correlation between EMT and gastric cancer TICs， and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail， E-cadherin， N-cadherin， and CD133 may be effectively predict the prognosis of gastric cancer patients.
Objective To study the expression of human Runt-related transcription factor 1 (RUNX1) in rat airway epithelial cells stimulated by cigarette smoking extract (CSE), and explore the role of RUNX1 in regulating epithelial-mesenchymal transition (EMT). Methods Primary rat bronchial epithelial cells were cultured by enzyme digestion and stimulated with different concentrations of CSE. The viability of cells was detected by CCK-8 to explore the appropriate concentration of CSE. After the cells were treated with CSE, the Runx1 interference and overexpression vectors were constructed and transfected into the cells to silence or overexpress the Runx1 gene. Immunocytochemical method was used to detect RUNX1 expression and Western blot analysis was used to detect the expression of RUNX1, nuclear factor-κB (NF-κB), Snail, E-cadherin, and vimentin. Results The survival rate of bronchial epithelial cells could be reduced by CSE, and the degree of reduction was directly positively correlated to the concentration of CSE. After CSE stimulation, the expression level of E-cadherin in primary rat bronchial epithelial cells decreased significantly (P<0.05); the expression levels of RUNX1, NF-κB, Snail and vimentin significantly increased (P<0.05). After interfering with RUNX1 gene, the expression level of E-cadherin was up-regulated (P<0.05), and the expression levels of NF-κB, Snail and vimentin were down-regulated (P<0.05). After overexpression of RUNX1 gene, the expression level of E-cadherin decreased (P<0.05), and the expression levels of NF-κB, Snail and vimentin increased (P<0.05). Conclusions CSE promotes the expression of RUNX1 in rat airway epithelial cells. RUNX1 might regulate EMT process by involving in the regulation of NF-κB /Snail expression.