scholarly journals RNF152 Negatively Regulates mTOR Signalling and Blocks Cell Proliferation in the Floor Plate

2019 ◽  
Author(s):  
Minori Kadoya ◽  
Noriaki Sasai
Keyword(s):  
Cell Proliferation ◽  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Cell Number ◽  
Floor Plate ◽  
Proliferation Rate ◽  
Negative Regulator ◽  
Downstream Effector ◽  
Plate Cell ◽  
Mtor Signalling

AbstractThe neural tube is composed of a number of neural progenitors and postmitotic neurons distributed in a quantitatively and spatially precise manner. The floor plate, located in the ventral-most region of the neural tube, has a lot of unique characteristics, including a low cell proliferation rate. The mechanisms by which this region-specific proliferation rate is regulated remain elusive.Here we show that the activity of the mTOR signalling pathway, which regulates the proliferation of the neural progenitor cells, is significantly lower in the floor plate than in other domains of the embryonic neural tube. We identified the forkhead-type transcription factor FoxA2 as a negative regulator of mTOR signalling in the floor plate. We demonstrate that FoxA2 transcriptionally induces the expression of the E3 ubiquitin ligase RNF152, which together with its substrate RagA, regulates cell proliferation via the mTOR pathway. Silencing of RNF152 led to the aberrant upregulation of the mTOR signal and aberrant cell division in the floor plate. Taken together, the present findings suggest that floor plate cell number is controlled by the negative regulation of mTOR signalling through the activity of FoxA2 and its downstream effector RNF152.

scholarly journals The Estrogen-Occupied Estrogen Receptor Functions as a Negative Regulator to Inhibit Cell Proliferation Induced by Insulin/IGF-1: A Cell Context-Specific Antimitogenic Action of Estradiol on Rat Lactotrophs in Culture

Endocrinology ◽  
2002 ◽  
Vol 143 (7) ◽  
pp. 2750-2758 ◽  
Author(s):  
Kengo Kawashima ◽  
Koji Yamakawa ◽  
Wakaba Takahashi ◽  
Soichi Takizawa ◽  
Ping Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Proliferative Activity ◽  
Cell Number ◽  
Negative Regulator ◽  
Simultaneous Treatment ◽  
Wide Range ◽  
Dependent Inhibition ◽  
Context Specific ◽  
Basal Proliferation

Abstract Estrogens stimulate cell proliferation in typical estrogen-responsive tissues including the anterior pituitary gland. Here we report that 17-β estradiol (E2) has estrogen receptor-mediated mitogenic and antimitogenic actions on rat lactotrophs in primary culture, depending on the cell context. E2 did not affect basal proliferation at 2 d after treatment, but it increased it at 4 d. Insulin markedly increased proliferative activity, which was inhibited by simultaneous treatment with E2, even after only 2 d of treatment. This antimitogenic action on insulin-induced proliferation was also observed with other estrogens but not with nonestrogenic steroids. Treatment with antiestrogens in combination with E2 antagonized both the mitogenic and antimitogenic actions of E2. Antiestrogen treatment alone inhibited basal proliferation, and it mimicked the inhibitory action of E2 on insulin-induced proliferation with less potency. In parallel with cell proliferation, an insulin-induced increase in the cell number of cyclin D1-immunoreactive lactotrophs was inhibited by E2 treatment. Although the antimitogenic action of E2 was seen with a wide range of doses of insulin or IGF-1, proliferation was stimulated rather than inhibited by E2 when cells were treated with serum or forskolin/isobutylmethylxanthine instead of insulin, indicating a mitogen-specific, but not proliferative activity-dependent, inhibition by E2. The results of estrogen-occupied estrogen receptors as negative regulators of proliferation suggest a novel interaction between estrogen and growth factors in the regulation of proliferation in estrogen-responsive cells.

scholarly journals Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 1001-1016 ◽  
Author(s):  
M.D. Goulding ◽  
A. Lumsden ◽  
P. Gruss
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Expression Patterns ◽  
Primitive Streak ◽  
Floor Plate ◽  
Neural Patterning ◽  
Specific Expression ◽  
Early Effect

Members of the paired box (Pax) gene family are expressed in discrete regions of the developing central nervous system, suggesting a role in neural patterning. In this study, we describe the isolation of the chicken homologues of Pax-3 and Pax-6. Both genes are very highly conserved and share extensive homology with the mouse Pax-3 and Pax-6 genes. Pax-3 is expressed in the primitive streak and in two bands of cells at the lateral extremity of the neural plate. In the spinal cord, Pax-6 is expressed later than Pax-3 with the first detectable expression preceding closure of the neural tube. When the neural tube closes, transcripts of both genes become dorsoventrally restricted in the undifferentiated mitotic neuroepithelium. We show that the removal of the notochord, or implantation of an additional notochord, dramatically alter the dorsoventral (DV) expression patterns of Pax-3 and Pax-6. These manipulations suggest that signals from the notochord and floor plate regulate the establishment of the dorsoventrally restricted expression domains of Pax-3 and Pax-6 in the spinal cord. The rapid changes to Pax gene expression that occur in neural progenitor cells following the grafting of an ectopic notochord suggest that changes to Pax gene expression are an early effect of the notochord on spinal cord patterning.

scholarly journals Brain-derived neurotrophic factor increases cell number of neural progenitor cells derived from human induced pluripotent stem cells

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11388
Author(s):  
Panetha Pansri ◽  
Phetcharat Phanthong ◽  
Nopparat Suthprasertporn ◽  
Yindee Kitiyanant ◽  
Alisa Tubsuwan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Neurotrophic Factor ◽  
Neural Progenitor Cells ◽  
Cell Number ◽  
Induced Pluripotent

Background Several pieces of evidence from in vitro studies showed that brain-derived neurotrophic factor (BDNF) promotes proliferation and differentiation of neural stem/progenitor cells (NSCs) into neurons. Moreover, the JAK2 pathway was proposed to be associated with mouse NSC proliferation. BDNF could activate the STAT-3 pathway and induce proliferation in mouse NSCs. However, its effects on proliferation are not fully understood and JAK/STAT pathway was proposed to play a role in this activity. Methods In the present study, the effects of BDNF on cell proliferation and neurite outgrowth of Alzheimer’s disease (AD) induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs) were examined. Moreover, a specific signal transduction pathway important in cell proliferation was investigated using a JAK2 inhibitor (AG490) to clarify the role of that pathway. Results The proliferative effect of BDNF was remarkably observed as an increase in Ki-67 positive cells. The cell number of hNPCs was significantly increased after BDNF treatment represented by cellular metabolic activity of the cells measured by MTT assay. This noticeable effect was statistically shown at 20 ng/ml of BDNF treatment. BDNF, however, did not promote neurite outgrowth but increased neuronal cell number. It was found that AG490 suppressed hNPCs proliferation. However, this inhibitor partially decreased BDNF-induced hNPCs proliferation. These results demonstrated the potential role of BDNF for the amelioration of AD through the increase of AD-derived hNPCs number.

scholarly journals In Vitro Biocompatibility Evaluation of Nine Dermal Fillers on L929 Cell Line

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Vincenza Cannella ◽  
Roberta Altomare ◽  
Vincenza Leonardi ◽  
Laura Russotto ◽  
Santina Di Bella ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Medical Devices ◽  
L929 Cell ◽  
Cell Number ◽  
Proliferation Rate ◽  
Two Samples ◽  
Human Use ◽  
L929 Cell Line

Objective. Biomaterial research for soft tissue augmentation is an increasing topic in aesthetic medicine. Hyaluronic acid (HA) fillers are widely used for their low invasiveness and easy application to correct aesthetic defects or traumatic injuries. Some complications as acute or chronic inflammation can occur in patients following the injection. Biocompatibility assays are required for medical devices intended for human use, in order to prevent damages or injuries in the host. In this study, nine HA fillers were tested in order to evaluate their cytotoxicity and their effects on L929 cell line, according to the UNI EN ISO 10993 regulation. Methods. Extracts were prepared from nine HA fillers, and MTS viability assay was performed after 24 h, 48 h, and 72 h of exposure of cells to extracts. Cells cultured with HA filler extracts were monitored for up to 72 h, counted, and stained with haematoxylin/eosin in order to evaluate the cell proliferation rate and morphology. Results. None of the filler tested showed a cytotoxic effect. Two samples showed a higher vitality percentage and higher cell number while two samples showed a lower vitality percentage and lower cell number at 72 h. Conclusion. Data obtained suggest that although examined fillers are not cytotoxic, they show different effects on the in vitro cell proliferation rate. In vitro studies of medical devices could lead to important implications since these could aid to predict effects about their in vivo application. These easy and rapid assays could be useful to test new materials intended for human use avoiding animal tests.

miRNA-489-3p Improves Sepsis-Induced Lung Injury by Regulating Toll-Like Receptor 4 (TLR4) Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1722-1729
Author(s):  
Xiaowei He ◽  
Longgang Shao ◽  
Min Xu ◽  
Tan Li ◽  
Namin Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Injury ◽  
Cell Number ◽  
Nuclear Volume ◽  
Proliferation Rate ◽  
Luciferase Reporter ◽  
Toll Like Receptor 4 ◽  
Apoptosis Rate ◽  
Cell Proliferation Rate ◽  
Vitro Model

Aim: To discuss miRNA-489-3p in sepsis-induced lung injury. Materials and methods: Using NR-8383 as research cell in our study, and using LPS stimulation to sepsis induced lung injury vitro model. Measuring cell proliferation by MTS assay; using Elisa assay to measure IL-1β, IL-6 and TNF-α concentration; apoptosis cell number and apoptosis rate were evaluated using TUNEL and flow cytometry; gene and protein were measured by RT-PCR and WB assay; measuring p-NF-κB(p65) nuclear volume by Immunofluorescence (IF); using Luciferase reporter assay to analysis miRNA-489-3p and TLR4 correlation. Results: Cell proliferation rate significantly down-regulated (P < 0.001), apoptosis cell number and apoptosis rate significantly increased (P < 0.001); IL-1β, IL-6 and TNF-α concentrations significantly up-regulated (P < 0.001); TLR4 and MyD88 gene and protein significantly increased (P < 0.001), NF-κB(p65) mRNA and p-NF-κB(p65) protein and nuclear volume significantly increased (P < 0.001). However, with miRNA-489-3p supplement, the cell proliferation rate, apoptosis cell number and apoptosis rate were significantly improved (P < 0.001, respectively) via TLR4, MyD88 and NF-κB(p65) mRNA and protein significantly depressing (P < 0.001, respectively). By LUC assay, miRNA-489-3p could target to TLR4 in NR-8383 cell. Conclusion: miRNA-489-3p overexpression had effect to improve sepsis induced lung injury via regulation TLR4/MyD88/NF-κB(p65).

scholarly journals Effect of miR-302b MicroRNA Inhibition on Chicken Primordial Germ Cell Proliferation and Apoptosis Rate

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 82
Author(s):  
Bence Lázár ◽  
Nikolett Tokodyné Szabadi ◽  
Mahek Anand ◽  
Roland Tóth ◽  
András Ecker ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Cell Biology ◽  
Primordial Germ Cell ◽  
Control Cell ◽  
Cell Number ◽  
Proliferation Rate ◽  
Slight Reduction ◽  
Apoptotic Cells ◽  
Dual Inhibition

The primordial germ cells (PGCs) are the precursors for both the oocytes and spermatogonia. Recently, a novel culture system was established for chicken PGCs, isolated from embryonic blood. The possibility of PGC long-term cultivation issues a new advance in germ cell preservation, biotechnology, and cell biology. We investigated the consequence of gga-miR-302b-5P (5P), gga-miR-302b-3P (3P) and dual inhibition (5P/3P) in two male and two female chicken PGC lines. In treated and control cell cultures, the cell number was calculated every four hours for three days by the XLS Imaging system. Comparing the cell number of control and treated lines on the first day, we found that male lines had a higher proliferation rate independently from the treatments. Compared to the untreated ones, the proliferation rate and the number of apoptotic cells were considerably reduced at gga-miR-302b-5P inhibition in all PGC lines on the third day of the cultivation. The control PGC lines showed a significantly higher proliferation rate than 3P inhibited lines on Day 3 in all PGC lines. Dual inhibition of gga-miR-302b mature miRNAs caused a slight reduction in proliferation rate, but the number of apoptotic cells increased dramatically. The information gathered by examining the factors affecting cell proliferation of PGCs can lead to new data in stem cell biology.

scholarly journals Cannabinoid Receptor Modulation of Neurogenesis: ST14A Striatal Neural Progenitor Cells as a Simplified In Vitro Model

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1448
Author(s):  
Erika Cottone ◽  
Valentina Pomatto ◽  
Stefania Rapelli ◽  
Rosaria Scandiffio ◽  
Ken Mackie ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
In Vitro Model ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Cell Number ◽  
Receptor Modulation ◽  
Vitro Model

The endocannabinoid system (ECS) is involved in the modulation of several basic biological processes, having widespread roles in neurodevelopment, neuromodulation, immune response, energy homeostasis and reproduction. In the adult central nervous system (CNS) the ECS mainly modulates neurotransmitter release, however, a substantial body of evidence has revealed a central role in regulating neurogenesis in developing and adult CNS, also under pathological conditions. Due to the complexity of investigating ECS functions in neural progenitors in vivo, we tested the suitability of the ST14A striatal neural progenitor cell line as a simplified in vitro model to dissect the role and the mechanisms of ECS-regulated neurogenesis, as well as to perform ECS-targeted pharmacological approaches. We report that ST14A cells express various ECS components, supporting the presence of an active ECS. While CB1 and CB2 receptor blockade did not affect ST14A cell number, exogenous administration of the endocannabinoid 2-AG and the synthetic CB2 agonist JWH133 increased ST14A cell proliferation. Phospholipase C (PLC), but not PI3K pharmacological blockade negatively modulated CB2-induced ST14A cell proliferation, suggesting that a PLC pathway is involved in the steps downstream to CB2 activation. On the basis of our results, we propose ST14A neural progenitor cells as a useful in vitro model for studying ECS modulation of neurogenesis, also in prospective in vivo pharmacological studies.

scholarly journals Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

2021 ◽  
Vol 22 (8) ◽  
pp. 3804
Author(s):  
Luisa Siculella ◽  
Laura Giannotti ◽  
Benedetta Di Chiara Stanca ◽  
Matteo Calcagnile ◽  
Alessio Rochira ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Negative Correlation ◽  
Cancer Biology ◽  
Human Tumor ◽  
In Silico Analysis ◽  
Proliferation Rate ◽  
Reactive Intermediate ◽  
Cell Proliferation Rate

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.

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