scholarly journals Regulation of cell quiescence-proliferation balance by Ca2+-CaMKK-Akt signaling

2021 ◽  
Author(s):  
Yi Xin ◽  
Jian Guan ◽  
Yingxiang Li ◽  
Cunming Duan
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Ryanodine Receptors ◽  
Akt Signaling ◽  
Imaging Studies ◽  
Signaling Mechanism ◽  
Cell Quiescence ◽  
Initial Decrease ◽  
Genetic Deletion ◽  
Dependent Mechanism

Compared with our extensive understanding of the cell cycle, we have limited knowledge of how the cell quiescence-proliferation decision is regulated. Using a zebrafish epithelial model, we report a novel signaling mechanism governing the cell quiescence-proliferation decision. Zebrafish Ca2+-transporting epithelial cells or ionocytes maintain high cytoplasmic Ca2+ levels ([Ca2+]c) due to the expression of Trpv6. Genetic deletion, pharmacological inhibition of Trpv6 or reducing external Ca2+ lowered the [Ca2+]c and reactivated these cells. The ionocyte reactivation was attenuated by chelating intracellular Ca2+ and inhibiting calmodulin (CaM), suggesting a Ca2+/CaM-dependent mechanism at work. Ling-term imaging studies showed that after an initial decrease, [Ca2+]c gradually returned to the basal levels. There was a concomitant decease in ER Ca2+ levels. Lowering the ER Ca2+ store content or inhibiting ryanodine receptors impaired ionocyte reactivation. Further analyses suggest that CaMKK is a key molecular link between Ca2+ and Akt signaling. Genetic deletion or inhibition of CaMKK abolished and expression of a constitutively active Akt rescued cell reactivation. These results suggest that the quiescence-proliferation decision in zebrafish ionocytes is regulated by Trpv6-mediated Ca2+ and CaMKK-Akt signaling.

scholarly journals The proliferative effect of cortisol on bovine endometrial epithelial cells

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Junsheng Dong ◽  
Jun Li ◽  
Jianji Li ◽  
Luying Cui ◽  
Xia Meng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Akt Signaling ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Physiological Level ◽  
Endometrial Epithelial Cells

Abstract Background Bovine endometrial epithelial cells (BEECs) undergo regular regeneration after calving. Elevated cortisol concentrations have been reported in postpartum cattle due to various stresses. However, the effects of the physiological level of cortisol on proliferation in BEECs have not been reported. The aim of this study was to investigate whether cortisol can influence the proliferation properties of BEECs and to clarify the possible underlying mechanism. Methods BEECs were treated with different concentrations of cortisol (5, 15 and 30 ng/mL). The mRNA expression of various growth factors was detected by quantitative reverse transcription-polymerase chain reaction (qPCR), progression of the cell cycle in BEECs was measured using flow cytometric analysis, and the activation of the Wnt/β-catenin and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways was detected with Western blot and immunofluorescence. Results Cortisol treatment resulted in upregulated mRNA levels of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF); however, it had no influence on transforming growth factor-beta1 (TGF-β1). Cortisol (15 ng/mL) accelerated the cell cycle transition from the G0/G1 to the S phase. Cortisol upregulated the expression of β-catenin, c-Myc, and cyclinD1 and promoted the phosphorylation of PI3K and AKT. Conclusions These results demonstrated that cortisol may promote proliferation in BEECs by increasing the expression of some growth factors and activating the Wnt/β-catenin and PI3K/AKT signaling pathways.

Activation of G Protein-coupled Receptor 30 Promotes Proliferation of Goat Mammary Epithelial Cells via MEK/Erk&PI3K/Akt Signaling Pathway

2020 ◽  
Author(s):  
Ying Zhao ◽  
Haokun Liu ◽  
Mingzhen Fan ◽  
Yuyang Miao ◽  
Xiaoe Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Cyclin D1 ◽  
Mammary Epithelial Cells ◽  
Cyclin B1 ◽  
Akt Signaling ◽  
Mammary Epithelial ◽  
M Phase ◽  
G Protein Coupled ◽  
Goat Mammary Epithelial Cells

Abstract BackgroundGoat is an important dairy animal. During lactation, maintaining a high proliferative activity in goat mammary epithelial cells (GMECs) is significant to improve the yield and composition of goat milk. Estrogen is an essential hormone in epithelial cell proliferation and ductal morphogenesis of mammary gland. G protein-coupled receptor 30 (GPR30) is a novel membrane receptor of estrogen. However, the relationship between estrogen/GPR30 signaling and proliferation of goat mammary epithelial cells has not been reported. And the molecular mechanisms underlying the proliferative effect of estrogen via GPR30 on GMECs remain unclear.ResultsTo investigate the effect of estrogen/GPR30 signaling on GMECs proliferation, goat mammary epithelial cells, which expressed cytokeratin 18 and β-casein, were isolated and identified, defining their mammary alveolar epithelium origination. Estrogen and GPR30 agonist G1 obviously promoted the proliferation of GEMCs, in contrast, GPR30 antagonist G15 partly abolished estrogen-induced cell proliferation. Remarkably, the stimulatory effect of estrogen and G1 on GMECs growth was suppressed by GPR30 knockdown detected by cell counting assay, CCK-8 assay, and BrdU assay, suggesting that estrogen/GPR30 signaling was involved in GMECs proliferation. Additionally, G15 decreased cyclin D1, cyclin B1, CDK1, and p-CDK1 expression, resulting in cell cycle arrest in the G2/M phase via a down-regulated phosphorylation of Erk1/2 and Akt compared with estrogen alone. What’s more, knock-down GPR30 led to an accumulation in the G2/M phase and inhibition of cyclin D1, cyclin B1, CDK1, and p-CDK1 expression via a down-regulation of phosphorylated Erk1/2 and Akt despite the presence of estrogen and G1. Furthermore, MEK inhibitor and PI3K inhibitor decreased the expression of cyclin D1, cyclin B1, CDK1, and p-CDK1, and repressed estrogen-induced and G1-driven promotion of cell growth. It indicated that estrogen/GPR30 signaling played an important role in GMECs proliferation by affecting cell cycle progression via MEK/Erk&PI3K/Akt signaling pathway.ConclusionThis study may provide a new insight into the effect of estrogen/GPR30 signaling on the regulatory action of goat mammary gland development.

scholarly journals Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

2020 ◽  
Author(s):  
zhongli wang ◽  
chao liu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Akt Signaling ◽  
Gastric Epithelial Cells ◽  
Akt Signaling Pathway ◽  
Potential Therapeutic Target ◽  
Cycle Arrest

Abstract Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice.Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

scholarly journals Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

2020 ◽  
Author(s):  
zhongli wang ◽  
chao liu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Akt Signaling ◽  
Gastric Epithelial Cells ◽  
Akt Signaling Pathway ◽  
Potential Therapeutic Target ◽  
Cycle Arrest

Abstract Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice. Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p < 0.05), while the levels of PI3K were notably increased (p < 0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p < 0.05), where circRNA_100269 and PI3K was inversely correlated (p < 0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p < 0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p < 0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p < 0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p < 0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

scholarly journals Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

2020 ◽  
Author(s):  
zhongli wang ◽  
chao liu
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Akt Signaling ◽  
Gastric Epithelial Cells ◽  
Akt Signaling Pathway ◽  
Potential Therapeutic Target ◽  
Cycle Arrest

Abstract Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice. Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

scholarly journals Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway

2021 ◽  
Author(s):  
Karolina Kowalska ◽  
Marta Justyna Kozieł ◽  
Dominika Ewa Habrowska-Górczyńska ◽  
Kinga Anna Urbanek ◽  
Kamila Domińska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Damage ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cycle Phase ◽  
Akt Signaling Pathway ◽  
Normal Prostate ◽  
Prostate Epithelial Cells

AbstractPhosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.

scholarly journals Luminal-Applied Flagellin Is Internalized by Polarized Intestinal Epithelial Cells and Elicits Immune Responses via the TLR5 Dependent Mechanism

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24869 ◽  
Author(s):  
Tonyia Eaves-Pyles ◽  
Heng-Fu Bu ◽  
Xiao-di Tan ◽  
Yingzi Cong ◽  
Jignesh Patel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Dependent Mechanism

scholarly journals Effects of Aspergillus fumigatus Conidia on Apoptosis and Proliferation in an In Vitro Model of the Lung Microenvironment

2021 ◽  
Vol 9 (7) ◽  
pp. 1435
Author(s):  
Hisako Kushima ◽  
Toshiyuki Tsunoda ◽  
Taichi Matsumoto ◽  
Yoshiaki Kinoshita ◽  
Koichi Izumikawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Aspergillus Fumigatus ◽  
Rna Sequencing ◽  
A549 Cells ◽  
Western Blots ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Nih 3T3

Background/Aim: Aspergillus is often detected in respiratory samples from patients with chronic respiratory diseases, including pulmonary fibrosis, suggesting that it can easily colonize the airways. To determine the role of Aspergillus colonization in pulmonary fibrosis, we cultured human lung epithelial A549 cells or murine embryo fibroblast NIH/3T3 cells with Aspergillus conidia in 3D floating culture representing the microenvironment. Materials and Methods: Cells were cultured in two-dimensional (2D) and three-dimensional floating (3DF) culture with heat-inactivated Aspergillus fumigatus (AF) 293 conidia at an effector-to-target cell ratio of 1:10 (early-phase model) and 1:100 (colonization model), and RNA-sequencing and Western blots (WB) were performed. Results: AF293 conidia reduced A549 cell growth in 2D and 3DF cultures and induced apoptosis in A549 spheroids in 3DF culture. RNA-sequencing revealed the increased expression of genes associated with interferon-mediated antiviral responses including MX dymamin-like GTPase 1 (MX1). Interestingly, the decreased expression of genes associated with the cell cycle was observed with a high concentration of AF293 conidia. WB revealed that epithelial-mesenchymal transition was not involved. Notably, AF293 conidia increased NIH/3T3 growth only in 3DF culture without inducing an apoptotic reaction. RNA-sequencing revealed the increased expression of genes associated with interferon signalling, including MX2; however, the decreased expression of genes associated with the cell cycle was not observed. Conclusions: AF affects both apoptosis of epithelial cells and the growth of fibroblasts. A deeper understanding of the detailed mechanisms underlying Aspergillus-mediated signaling pathway in epithelial cells and fibroblasts will help us to understand the lung microenvironment.

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