scholarly journals IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

2017 ◽  
Vol 44 (1) ◽  
pp. 293-302 ◽  
Author(s):  
Meng Yang ◽  
Lei Wang ◽  
Xurong Wang ◽  
Xuezhi Wang ◽  
Zhiqiang Yang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Promoting Effect ◽  
Expression Levels ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Gene And Protein Expression

Background/Aims: Vascular endothelial growth factor (VEGF) has been demonstrated to play a pivotal role in the regulation of angiogenesis in ovarian follicular development, particularly during the preovulatory period. Although numerous studies have shown that interleukin-6 (IL-6) is one of the major inducing factors that regulate the expression of VEGF in non-ovarian cells, whether it involved in regulating the expression of VEGF in normal ovarian granulosa cells is still unknown. The aim of this study was to elucidate the mechanisms underlying the effect of IL-6 on FSH-induced VEGF expression in bovine granulosa cells derived from large follicles. Methods: VEGF mRNA expression in granulosa cells after IL-6 with/without inhibitors treatment was analyzed by RT-qPCR. Phosphorylation levels of ERK1/2 and STAT3 proteins induced by IL-6 were analyzed by western blotting. The protein levels produced by granulosa cells were detected by ELISA. Results: High concentration of IL-6 (10ng/ml) can significantly up-regulate FSH-induced VEGF gene and protein expression levels in granulosa cells, and also promote the VEGF upstream regulators HIF-1α and COX2 mRNA expression. VEGF expression levels were significantly decreased after specifically blocking HIF-1α and COX2 by using inhibitors. The up-regulation effect of IL-6 on FSH-induced VEGF expression in granulosa cells mainly through activating the JAK/STAT3 signaling pathway, which can be impaired by JAK inhibitors. Conclusion: IL-6 can promote FSH-induced VEGF expression in granulosa cells, which is mainly achieved by increasing the expression of HIF-1α and COX2.This promoting effect is mediated by activating the JAK/STAT3 pathway. Moreover, there may be a synergistic relationship between FSH and IL-6 in the regulation of VEGF expression.

Mechanism of interaction between TM4SF1 and jak2-stat3 signaling pathway in lung cancer cells and expression analysis in non-small cell lung cancer

2020 ◽  
Author(s):  
Yumeng Niu ◽  
Hailong Deng ◽  
Lipeng Li ◽  
Weikang Chen ◽  
Yuxuan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Normal Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Skin Cancers ◽  
Stat3 Signaling Pathway ◽  
Cancer Tissues

Abstract Background According to the latest data released in 2018, it is estimated that there will be 18.1 million new cancer cases worldwide (excluding 1.7 million non-melanoma skin cancers) and 9.6 million cancer deaths (excluding 950 non-melanoma skin cancers) Million cases). Among them, the incidence of lung cancer (11.6% of the total number of cases) and mortality (18.4% of the total number of cancer deaths, which are expected to cause 1.8 million deaths) are the first. In recent years, studies have found TM4SF1 play an important role in the development process of many tumors.Methods Sixty-one patients with NSCLC who underwent surgical resection of cancer tissues, para-carcinoma tissues, and 10 normal lung tissues removed from benign lung disease (Jun/2018-Dec/2018) were collected. Real-time immunofluorescence quantitative PCR (qRT-PCR) and Western blot were used to detect the expression of TM4SF1 in NSCLC tissues (CT), para-carcinoma tissue (PCT), and normal lung tissues(NLT). TM4SF1 gene was overexpressed in lung cancer A549 cells using lentiviral transfection technology, qRT-PCR and Western blot were used to detect whether TM4SF1 gene was successfully expressed in lung cancer A549 cells, and Transwell was used to detect the effect of TM4SF1 overexpression on A549 migration. JAK2-STAT3 signal pathway interference reagent AG490 was used to analyze the expression levels of Stat3 and downstream Sox2 genes in the overexpression group, blank group, negative control group and their corresponding treatment groups TM4SF1, JAK2-STAT3 signal pathway using real-time qRT-PCR. Analyze the relevance of these three indicators at the same time.Results The expression levels of TM4SF1 mRNA and protein in cancer tissues were significantly higher than those in adjacent cancer tissues (P<0.05) and normal lung tissue specimens (P <0.05). The expression of TM4SF1 was not significantly associated with the age and sex of patients, but was associated with tumor size, degree of differentiation, lymph node metastasis, and clinical stage were related (P<0.05). TM4SF1 was successfully overexpressed in A549 cells. After overexpressing TM4SF1, the ability to migrate of A549 cells was significantly enhanced, and the expression levels of Stat3 and downstream Sox2 in the JAK2-STAT3 signaling pathway were up-regulated. The expression of TM4SF1, Stat3 and Sox2 at the mRNA level showed a positive correlation trend (P<0.01).Conclusion TM4SF1 is highly expressed in NSCLC, and its expression level is closely related to many clinical staging indicators. Overexpression of this gene can promote the migration of A549 cells and up-regulate the expression levels of Stat3 and downstream Sox2 in the JAK2-STAT3 signaling pathway. The expressions of TM4SF1, Stat3 and Sox2 were positively correlated in A549 cells. TM4SF1 may promote the occurrence, development and distant metastasis of NSCLC through this pathway. TM4SF1 may become a potential therapeutic target for NSCLC.

scholarly journals MicroRNA-21 Regulates the Proliferation, Differentiation, and Apoptosis of Human Renal Cell Carcinoma Cells by the mTOR-STAT3 Signaling Pathway

2016 ◽  
Vol 24 (5) ◽  
pp. 371-380 ◽  
Author(s):  
Tao Liang ◽  
Xiao-Yong Hu ◽  
Yong-Hui Li ◽  
Bin-Qiang Tian ◽  
Zuo-Wei Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Caspase 3 ◽  
Human Renal Cell Carcinoma ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

MicroRNA-21 (miRNA-21), a kind of short, noncoding RNAs, functioned as a tumor marker and was upregulated in renal cell carcinoma (RCC). However, the underlying mechanisms of miRNA-21 in RCC were uncertain. Therefore, the effects and mechanisms of miRNA-21 on the proliferation, differentiation, and apoptosis of cultured human RCC cells were further investigated in this study. After slicing miRNA-21 in RCC cells, the viability, mRNA expression of C/EBPα and PPARγ, caspase 3 activity, and protein expression of mTOR, STAT3, and pSTAT3 were determined. It was found that knockdown of miRNA-21 downregulated the optical density (OD) value of cells, inhibited mRNA expression of PPARγ and C/EBPα, and enhanced activity of caspase 3. Furthermore, protein expression of pSTAT3 was also decreased in the absence of miRNA-21. Notably, miRNA-21-changed proliferation, differentiation, and apoptosis of human RCC cells were partially regulated following the block of the mTOR-STAT3 signaling pathway by the mTOR inhibitor (XL388). It was indicated that miRNA-21 promoted proliferation and differentiation and decreased apoptosis of human RCC cells through the activation of the mTOR-STAT3 signaling pathway.

scholarly journals Adiponectin Enhances Biological Functions of Vascular Endothelial Progenitor Cells Through the mTOR-STAT3 Signaling Pathway

2018 ◽  
pp. 563-570 ◽  
Author(s):  
X. DONG ◽  
X. YAN ◽  
W. ZHANG ◽  
S. TANG
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Vascular Endothelial ◽  
Biological Functions ◽  
Endothelial Progenitor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Adiponectin (APN), an adipose tissue-excreted adipokine, plays protective roles in metabolic and cardiovascular diseases. In this study, the effects and mechanisms of APN on biological functions of rat vascular endothelial progenitor cells (VEPCs) were investigated in vitro. After administrating APN in rat VEPCs, the proliferation was measured by methyl thiazolyl tetrazolium (MTT) method, the apoptotic rate was test by Flow cytometry assay, mRNA expression of B-cell lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression of mechanistic target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) was analyzed by Western blot. It was suggested that APN promoted the optical density (OD) value of VEPCs, enhanced mRNA expression of Bcl-2 and VEGF, and inhibited cell apoptotic rate. Furthermore, protein expression of pSTAT3 was also increased in the presence of APN. Moreover, APN changed-proliferation, apoptosis and VEGF expression of VEPCs were partially suppressed after blocking the mTOR-STAT3 signaling pathway by the mTOR inhibitor XL388. It was indicated that APN promoted biological functions of VEPCs through targeting the mTOR-STAT3 signaling pathway.

scholarly journals Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xiao-Juan Xie ◽  
Dong-Mei Fan ◽  
Kai Xi ◽  
Ya-Wei Chen ◽  
Peng-Wei Qi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Inhalation Anesthesia ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Myocardial Ischemia Reperfusion

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.

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