scholarly journals Low Expression of STING Promoted Endometrial Stromal Cells Invasion and Migration Via STING/IRF3/IFNb1 Pathway in Endometriosis Eutopic Endometrium

2021 ◽  
Author(s):  
zhen xu ◽  
hen zhao ◽  
caixin yue ◽  
lixia zhang ◽  
muzi li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stromal Cells ◽  
Chronic Inflammatory Disease ◽  
Glandular Epithelium ◽  
Normal Endometrium ◽  
Endometrial Stromal Cells ◽  
Eutopic Endometrium ◽  
Invasion And Migration ◽  
And Migration ◽  
Low Expression

Abstract Background: Recent studies have confirmed that endometriosis is a chronic inflammatory disease. In our previous work, we found that STING (stimulator of interferon genes) was differentially expressed in eutopic endometrium and controlled endometrium by proteomics.Method: we used the 11 pairs of samples to verify STING expression by WB and IHC experiments. We detected cells proliferation by EdU assays, cells invasion and migration by Transwell assays. The effect of signaling pathway in HESC was detected by WB and Elisa expreriments.Results: STING was significantly lower expressed in eutopic endometrium of endometriosis, while IHC results showed that STING was expressed in both stroma and glandular epithelium of normal endometrium, but in endometriosis, STING was mainly expressed in the stroma of eutopic endometrium, and mainly in glandular epithelium of ectopic endometrium. Further study on the role of STING on endometrial stromal cells showed that low expression of STING could promote the HESC proliferation by EdU experiments, invasion and migration by Transwell experiments. The effect of STING/IRF3/IFNb1 signaling pathway in HESC with low expression of STING was also reduced, mainly showed the decreased expression of phosphorylated IRF3 and TBK1, and the decreased secretion of IFNb1. In order to further study the effect of IFNb1, secreted by STING/ IRF3/IFNb1 signaling pathway, on stromal cells, we added exogenous IFNb1 to the HESC with low expression of STING, and found that IFNb1 could reverse the invasion and migration function of stromal cells, but little effect on cell proliferation.Conclusions: We clarified that STING expressed mainly in stromal tissues and lower in endometriosis eutopic endometrium compared to normal endometrium. Low expressed STING promoted stromal cells invasion and migration via STING/IRF3/IFNb1 signaling pathway.

scholarly journals T-cadherin inhibits invasion and migration of endometrial stromal cells in endometriosis

2019 ◽  
Vol 35 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Qinsheng Lu ◽  
Yanqing Huang ◽  
Jiabao Wu ◽  
Yutao Guan ◽  
Miaomiao Du ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Invasion ◽  
Stromal Cells ◽  
Medical Center ◽  
Guangdong Province ◽  
Endometrial Stromal Cells ◽  
Eutopic Endometrium ◽  
Invasion And Migration ◽  
And Migration

Abstract STUDY QUESTION What is the expression level of T-cadherin in endometriosis, and does T-cadherin play a role in regulating invasion and migration of endometrial stromal cells? SUMMARY ANSWER T-cadherin expression was reduced in ectopic endometriotic lesions compared to eutopic endometrium, and T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells. WHAT IS KNOWN ALREADY Endometriosis is a disease that involves active cell invasion and migration. T-cadherin can inhibit cell invasion, migration and proliferation in various cancer cells, but its role in endometriosis has not been investigated. STUDY DESIGN, SIZE, DURATION We explored the expression status of T-cadherin in 40 patients with and 24 without endometriosis. We also isolated endometrial stromal cells to study the invasion, migration and signaling pathway regulation of T-cadherin overexpression. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were recruited at the Guangzhou Women and Children’s Medical Center to study the expression levels of T-cadherin. The expression of T-cadherin was detected by immunohistochemistry staining and western blot. H-score was used to evaluate the staining intensity of T-cadherin. The correlation between T-cadherin expression levels (H-score) and endometriosis patients’ age, stage, lesion size and adhesion was analyzed. Endometrial stromal cells from patients with and without endometriosis were isolated, and cell invasion and migration were detected by transwell assays after T-cadherin overexpression. The expression of vimentin in T-cadherin-overexpressed cells was detected by western blot. After T-cadherin overexpression, the phosphorylation profile of signaling pathway proteins was detected with the Proteome Profiler Human Phospho-Kinase Array Kit. MAIN RESULTS AND THE ROLE OF CHANCE There was no difference in the expression of T-cadherin in the normal endometrium of control patients and the eutopic endometrium of endometriotic patients, but it was significantly decreased in the ectopic endometrium of endometriotic patients, compared with control endometrium and eutopic endometrium of endometriosis patients (P < 0.0001, for both). Western blot analysis also showed that the expression of T-cadherin was decreased in ectopic endometriotic lesions, but not the normal control endometrium or the endometriotic eutopic endometrium. The results of transwell assays indicated that T-cadherin overexpression inhibited the invasion and migration of endometrial stromal cells. In addition, T-cadherin overexpression promoted the phosphorylation of HSP27 (S78/S82) and JNK 1/2/3 (T183/Y185, T221/Y223) and decreased the expression of vimentin, MMP2 and MMP9 in eutopic endometriosis stromal cells. LARGE-SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The control group were patients with benign gynecological conditions (e.g. uterus myoma, endometrial or cervical polyp), which may have genetic or epigenetic variations associated with T-cadherin expression and signaling pathways. The case numbers of involved endometriosis and control patients were limited. This study only used endometrial stromal cells from patients with or without endometriosis. Ideally, ectopic endometrial stromal cells of the ovarian endometriotic lesions should also be utilized to explore the function of T-cadherin. WIDER IMPLICATIONS OF THE FINDINGS Further investigation of the role of T-cadherin in endometriosis may generate new potential therapeutic targets for this complex disorder. STUDY FUNDING AND COMPETING INTEREST(S) This study was supported by the Natural Science Foundation of Guangdong Province (2016A030313495), National Natural Science Foundation of China (81702567, 81671406, 31871412), the Science and Technology Programs of Guangdong (2017A050501021), Medical Science Technology Research Fund of Guangdong Province (A2018075), the Science and Technology Programs of Guangzhou City (201704030103), Internal Project of Family Planning Research Institute of Guangdong Province (S2018004), Post-doc initiation fund of Guangzhou (3302) and Post-doc science research initiation fund of Guangzhou Women and Children’s Medical Center (20160322). There are no conflicts of interest.

scholarly journals USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway

2018 ◽  
Vol 315 (6) ◽  
pp. C863-C872 ◽  
Author(s):  
Qiong Chen ◽  
Yuanyuan Hang ◽  
Tingting Zhang ◽  
Li Tan ◽  
Shuangdi Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Uterine Cavity ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Erk Pathway ◽  
Endometrial Stromal Cells ◽  
And Migration ◽  
Proliferation And Migration

Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. The mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis, and migration has been found to be activated in endometriosis. However, regulation of the MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis, and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-small-interfering RNA (siRNA) or pLVX-Puro-USP10 with or without MEK inhibitor PD-98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry, and Transwell, respectively. The gene and protein expressions were measured by real-time PCR or Western blot. USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK/ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD-98059. USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not mRNA expression, through deubiquitination. In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

scholarly journals MicroRNA-342 Promotes the Malignant-Like Phenotype of Endometrial Stromal Cells via Regulation of Annexin A2

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Dan Sun ◽  
Yiting Wang ◽  
Li Wang ◽  
Xin Guo
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Annexin A2 ◽  
Mtor Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Normal Endometrium ◽  
Endometrial Stromal Cells

The relevance of miRNA- (miR-) 342 to endometriosis has been highlighted, while its function in regulating the malignant-like phenotype of endometrial stromal cells which demonstrate epigenetic abnormalities that alter expression of transcription factors, remains unclear. Therefore, we sought to characterize the effects of miR-342 in endometrial stromal cell proliferation by regulating Annexin A2 (ANXA2). We first characterized the levels of miR-342 and ANXA2 in 31 cases of normal endometrium from patients with grade II-III cervical intraepithelial neoplasia or patients with hysterectomy versus ectopic endometrial tissues of 42 patients with endometriosis. miR-342 was upregulated, while ANXA2 was downregulated in ectopic endometrial tissues. Bioinformatics website and dual-luciferase reporter assay revealed that miR-342 negatively modulated ANXA2 expression. Following loss- and gain-of-function approaches, CCK-8, Transwell, and flow cytometry demonstrated that overexpression of miR-342 markedly increased cell proliferation, migration, and invasion but inhibited cell apoptotic ratio of endometrial stromal cells, which was reversed by ANXA2 elevation. Further, overexpressed miR-342 activated the PI3K/AKT/mTOR signaling pathway, as evidenced by upregulated levels of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Taken together, miR-342 targets ANXA2 to activate the PI3K/AKT/mTOR signaling pathway, thereby promoting the malignant-like phenotype of endometrial stromal cells, highlighting miR-342 inhibition as a promising approach for the treatment of endometriosis.

miR-340 Inhibits the Development of Hepatocellular Carcinoma by Down-Regulating Akt Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1785-1791
Author(s):  
Tangpeng Xu ◽  
Changli Ruan ◽  
Xu Bin ◽  
Mengxue Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Pathological Grade ◽  
Akt Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation Ability ◽  
And Migration ◽  
Cancer Tissues

Hepatocellular carcinoma (HCC) is a serious threat to human health. miR-340 participates in HCC pathogenesis, but its specific mechanism is not completely clear. Therefore, our study assessed the mechanism by how miR-340 involves in HCC. The cancer tissues and paracancerous tissues of HCC patients were collected. miR-340 mimics/NC and Akt siRNA were transfected into HepG2 cells followed by analysis of miR-304 and EMT-related molecules expression by Real-time PCR, cell invasion and migration by Transwell assay, cell proliferation ability by CCK8 assay as well as p-Akt and p-mTOR level by Western blot. miR-340 in HCC tissues was significantly downregulated compared to adjacent tissues (P <0.001). With increased pathological grade, miR-340 expression was decreased gradually. p-Akt and p-mTOR in HCC tissues was significantly upregulated and elevated gradually with increased pathological grade. p-Akt and p-mTOR was negatively associated with miR-340 (P <0.001). After overexpression of miR-340, HepG2 cell proliferation, invasion, migration and epithelialization were significantly inhibited, and p-Akt and p-mTOR was reduced. When Akt expression was interfered with siRNA, cell proliferation and epithelialization was further inhibited. miR-340 inhibits the development of hepatocellular carcinoma through Akt signaling pathway.

scholarly journals Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κκB signaling pathway

2022 ◽  
Vol 50 (1) ◽  
pp. 92-98
Author(s):  
Zhongxiang Fan ◽  
Dan Tang ◽  
Qiang Wu ◽  
Qun Huang ◽  
Jie Song ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Signaling Pathway ◽  
Airway Smooth Muscle ◽  
Airway Remodeling ◽  
Muscle Cells ◽  
Chronic Inflammatory Disease ◽  
Migration And Invasion ◽  
Airway Smooth Muscle Cells ◽  
And Migration

Background: Asthma is a common chronic inflammatory disease of the airway, and airway remodeling and the proliferation mechanism of airway smooth muscle cells (ASMCs) is of great significance to combat this disease.Objective: To assess possible effects of scopoletin on asthma and the potential signaling pathway.Materials and methods: ASMCs were treated PDGF-BB and scopoletin and subjected to cell viability detection by CCK-8 assay. Cell migration of ASMCs was determined by a wound closure assay and transwell assay. The protein level of MMP2, MMP9, calponin and α-SMA were measured using western blot. The levels of NF-κB signaling pathway were detected by Western blotting.Results: Scopoletin inhibited proliferation of PDGF-BB - induced ASMCs. Also it suppressed the migration and invasion of PDGF-BB - induced ASMCs. We further showed that Scopoletin regulated phenotypic transition of ASMCs. Mechanically, Scopoletin inhibited proliferation and invasion of ASMCs by regulating NF-κB signaling pathway.Conclusions: We therefore thought Scopoletin could serve as a promising drug for the treatment of asthma.

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