scholarly journals P65 Targets FGFR1 to Regulate the Survival of Ovarian Granulosa Cells

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1334 ◽  
Author(s):  
Xiaolong Yuan ◽  
Zhonghui Li ◽  
Yaru Kong ◽  
Yuyi Zhong ◽  
Yingting He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Biological Effects ◽  
Follicular Development ◽  
Pi3k Signaling ◽  
Proliferation Markers ◽  
Promote Cell Proliferation ◽  
Protein Levels ◽  
Ovarian Granulosa Cells ◽  
Pi3k Signaling Pathway

In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the FGFR1 gene of the PI3K signaling pathway and the p65 subunit of the transcription factor NF-κB may regulate the proliferation and apoptosis of GCs involved in follicular development. However, little is known about whether p65 regulates the transcription of FGFR1, as well as the biological effects of p65 and FGFR1 on the survival of GCs and follicular development. In porcine follicles and GCs, we found that p65 and FGFR1 were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of p65 and FGFR1 significantly increased from small to large follicles. Both p65 and FGFR1 were found to activate the PI3K signaling pathway, and the expressions of proliferation markers (PCNA and MKI67) and the anti-apoptotic gene BCL2 were significantly increased by p65 and FGFR1. Furthermore, both p65 and FGFR1 were observed to promote cell proliferation and inhibit the cell apoptosis of GCs, and p65 was confirmed to bind at the −348/−338 region of FGFR1 to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of FGFR1. Taken together, p65 may target the −348/−338 region of FGFR1, promote the transcription of FGFR1, and enhance the pro-proliferation effect and anti-apoptotic effect of FGFR1 to facilitate the growth of follicles. This study will provide useful information for further investigations on the p65-mediated-FGFR1 signaling pathway during folliculogenesis in mammals.

scholarly journals KISS1 Suppresses Apoptosis and Stimulates the Synthesis of E2 in Porcine Ovarian Granulosa Cells

Animals ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 54 ◽  
Author(s):  
Xiaoping Xin ◽  
Zhonghui Li ◽  
Yuyi Zhong ◽  
Qingqing Li ◽  
Jiaying Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Pi3k Signaling ◽  
Mrna Levels ◽  
Ovarian Granulosa Cells ◽  
Estrogen Synthesis ◽  
Pi3k Signaling Pathway

Previous studies have strongly recommended that KISS-1 metastasis suppressor (KISS1) plays an essential gatekeeper of the initiation of reproductive maturation in mammals. However, KISS1 has been recently reported to highly express in ovarian granulosa cells (GCs). But the biological functionalities of KISS1 on cell apoptosis, cell cycle, and synthesis of estradiol-17β (E2) have not been explored in GCs. In this study, using porcine GCs as a cellular model, the overexpression plasmid of KISS1 was built to explore the biological effects of KISS1 on the PI3K signaling pathway, estrogen signaling pathway, cell apoptosis, cell cycle, and E2 secretion. We found that mRNA of KISS1 highly expressed in the ovary and significantly increased from immature to mature follicles in gilts. Overexpression of KISS1 could significantly increase the mRNA expression of PIK3CG, PIK3C1, and PDK1, and significantly decreased the mRNA levels of FOXO3, TSC2, and BAD of PI3K signaling pathway. Furthermore, results of the flow cytometry showed that overexpression of KISS1 significantly inhibited the apoptosis of GCs and decreased the percentage of GCs at G0/G1 phase of the cell cycle. Additionally, overexpression of KISS1 could increase the mRNA levels of Star, CYP17, 3B-HSD, 17B-HSD of estrogen synthesis signaling pathway, significantly increase the concentration of E2 in the supernatant of the cultured GCs, and up-regulate the mRNA expression levels of ESR1 and ESR2. These results suggested that KISS1 might suppress cell apoptosis through activating the PI3K signaling pathway and stimulate synthesis of E2 via boosting the estrogen synthesis signaling pathway. This study would be of great interests for exploring the biological functionalities of KISS1 in the folliculogenesis and sex steroid production of the ovaries in mammals.

scholarly journals STAT4 targets KISS1 to promote the apoptosis of ovarian granulosa cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yao Jiang ◽  
Xiaoping Xin ◽  
Xiangchun Pan ◽  
Ailing Zhang ◽  
Zhe Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Luciferase Assay ◽  
Pi3k Signaling ◽  
Mrna Levels ◽  
Ovarian Granulosa Cells ◽  
Potential Binding ◽  
Apoptotic Effect ◽  
Pi3k Signaling Pathway

Abstract Background In mammals, it is known that the estradiol-17β (E2) is mainly synthetized in ovarian granulosa cells (GCs), and the excessive apoptosis of GCs induces the follicular atresia. Many studies have implicated the essential role of KISS1, with the pro-synthetic effect of E2 and the anti-apoptotic effect on GCs, in the mammalian folliculogenesis, and several STAT4 potential binding sites were previously predicted on the promoter of KISS1 in pigs. However, the biological effects of STAT4 on GCs and the molecular regulation between STAT4 and KISS1 remained largely unknown. Methods Using the porcine GCs as the cellular model, the overexpression plasmid, small interfering RNA, 5′-deletion and luciferase assay were applied to investigate the molecular mechanisms for STAT4 regulating the expression of KISS1. Results In this study, the STAT4 negatively regulated the mRNA and protein levels of KISS1 in porcine GCs, and the mRNA level of STAT4 was observed to significantly decrease from immature to mature follicles, which was inversed with that of KISS1. The relative luciferase activity of KISS1 promoter was significantly increased with deletion of the fourth potential binding site (− 305/− 295), and ChIP further confirmed that the STAT4 bound at − 305/− 295 region of KISS1. Besides, the STAT4 significantly regulated the mRNA levels of PDK1, FOXO3 and TSC2 of PI3K signaling pathway to promote the cell apoptosis and the percentage of cells at G0/G1 phase of cell cycle in GCs. Alternatively, the STAT4 significantly decreased the mRNA levels of CYP17, 3B-HSD, 17B-33 HSD, ESR1, and ESR2, as well as the concentration of E2 in GCs. Furthermore, interfering with the expression of STAT4 was observed to significantly stimulate the pro-synthetic effect of E2 and anti-apoptotic effect of KISS1 in GCs. Conclusions Collectively, the STAT4 might directly target at − 305/− 295 region of KISS1 to negatively regulate the transcription of KISS1, promote the cell apoptosis via PI3K signaling pathway, suppress the synthesis of E2 through the estrogen signaling pathway in porcine GCs. These proposed works could provide useful insight in further investigations on the molecular functionalities of STAT4 and KISS1 in the folliculogenesis of mammals.

scholarly journals The PI3K signaling pathway mediates the biological effects of leptin

2010 ◽  
Vol 54 (7) ◽  
pp. 591-602 ◽  
Author(s):  
Jose Donato Jr. ◽  
Renata Frazão ◽  
Carol Fuzeti Elias
Keyword(s):  
Food Intake ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Leptin Receptor ◽  
Biological Effects ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
Electrophysiological Properties ◽  
Pi3k Signaling Pathway

The activation of the leptin receptor recruits several intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway. While some of the leptin-induced signaling pathways, such as the JAK2/STAT3 pathway, induce cellular responses primarily through changes in gene expression, the PI3K pathway affects cellular properties more rapidly, through post-translational changes such as protein phosphorylation. Accordingly, several studies have shown that the PI3K pathway is required for the acute effects of leptin, such as a leptin-induced decrease in food intake. Leptin signaling through PI3K also affects the electrophysiological properties of neurons, including changes in their membrane potential and firing rates. In this review, we summarize the recent advances in our understanding of the role played by the PI3K signaling pathway in controlling food intake and energy balance. In particular, we focus on the importance of the PI3K signaling pathway as a mediator of the effects of leptin on hypothalamic neurons.

Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

2017 ◽  
Vol 24 (13) ◽  
Author(s):  
Safieh Ebrahimi ◽  
Mina Hosseini ◽  
Soodabeh Shahidsales ◽  
Mina Maftouh ◽  
Gordon A. Ferns ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Therapeutic Strategy ◽  
Pi3k Signaling ◽  
Pi3k Signaling Pathway

scholarly journals BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells

2020 ◽  
Vol 15 (1) ◽  
pp. 501-510
Author(s):  
Bin Ma ◽  
Wenjia Guo ◽  
Meihui Shan ◽  
Nan Zhang ◽  
Binlin Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Nuclear Localization ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pi3k Pathway ◽  
Pi3k Signaling ◽  
T47d Cells ◽  
Pi3k Signaling Pathway ◽  
Hormone Sensitive

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

scholarly journals Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

2014 ◽  
Vol 58 (8) ◽  
pp. 833-837 ◽  
Author(s):  
Miriane de Oliveira ◽  
Regiane Marques Castro Olimpio ◽  
Maria Teresa De Sibio ◽  
Fernanda Cristina Fontes Moretto ◽  
Renata de Azevedo Mello Luvizotto ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Thyroid Hormone Receptor ◽  
Pi3k Pathway ◽  
Control Group ◽  
Pi3k Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Receptor Alpha ◽  
Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

Tu1402 All-Trans Retinoic Acid (ATRA) Stimulates SLC26A3 Activity in Intestinal Epithelial Cells via a PI3K Signaling Pathway

2015 ◽  
Vol 148 (4) ◽  
pp. S-880 ◽  
Author(s):  
Shubha Priyamvada ◽  
Arivarasu Natarajan Anbazhagan ◽  
Anoop Kumar ◽  
Tarunmeet Gujral ◽  
Alip Borthakur ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Intestinal Epithelial Cells ◽  
Pi3k Signaling ◽  
Intestinal Epithelial ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Pi3k Signaling Pathway
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