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 investigate the influence of hypoxia on pro-metastasis induced by epithelial-mesenchymal transition (EMT) of human lung adenocarcinoma.
MethodsThe human lung cancer cell line H460 was cultured in hypoxic condition and the morphologic changes of the cells were observed under the microscope. The EMT-related markers including E-cadherin and vimentin were detected by Western blot. Transwell migration assay and transwell invasion assay were employed to detect the migratory and invasive activity of cancer cells.
ResultsHypoxic induced morphological changes were consistent with the mesenchymal phenotype, such as an elongated fibroblastic morphology, and conversion from a tightly packed epithelial cobblestone pattern to a loosely packed scattered phenotype. Compared with the control group, hypoxic attenuated the quantity of E-cadhenrin, but increased vimentin, which resulted in promotion of migration and invasion of H460.
ConclusionHypoxia induces EMT in H460 and enhances the invasive and migratory abilities of lung cancer cells.
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 understand research progress of influence of claudins on proliferation and activation for breast cancer.
MethodThe relevant literatures of influence of claudins on proliferation and activation for breast cancer were retrieved and reviewed.
ResultsThe claudins had 24 members in mammals,claudin-13 was missing in human beings.Expression and distribution mode of the claudins possessed highly tissue-specific,and multiple proteins were expressed in many organizations.The expressions of claudins could be regulated from the levels of transcription and post-transcription,coordinately regulated by the transcription factor and post-synthetic modifications.Claudins were related to epithelial-mesenchymal transition.Now the studies were relatively clear those focused on claudin-1,-2,-4,-6,and other subtypes,and the expression of claudin-1 indicated the poor prognosis of tumor;claudin-2 was closely related to liver metastasis of breast cancer;claudin-4 was closely related to triple negative breast cancer;the function of claudin-6 in the breast cancer was controversial.In addition to the claudins mentioned above,other claudin members also played certain roles in normal breast and malignant breast tumors.Claudin-5 might participate in metastasis of breast cancer through N-WASP and ROCK signal pathway;CD-24 and claudin-7 immunodepression had a certain guiding significance on prognosis of invasive ductal carcinoma;the expressions of claudin-16 and HAPLN3 gene were remarkably increased in human breast cancer;Claudin-20 induced breast cancer cells into a subtype that possessed the high invasiveness and weakened the resis-tance of epithelial-mesenchymal transition.Recently,the claudin-low subtype was proposed,and it differed from other types of breast cancer in many aspects,and also it had a better prognosis than other types of triple negative breast cancer.
ConclusionsClaudin,being an important member of tight junction protein,is confirmed to be related to epithelial-mesenchymal transition.Claudins play important roles in dissociaton,activation,invasiveness,and metastasis of breast cancer,but there is no final conclusion which member contributes to invasiveness and metastasis of breast cancer.Moreover,there are opposite conclusions on some certain claudins members in breast cancer which might due to the different subtypes of breast cancer,so,further studies about the function of claudins in different subtypes are needed eagerly.
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.
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.
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 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.
