scholarly journals Differential Modulation of Matrix Metalloproteinases-2 and -7 in LAM/TSC Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1760
Author(s):  
Silvia Ancona ◽  
Emanuela Orpianesi ◽  
Clara Bernardelli ◽  
Eloisa Chiaramonte ◽  
Raffaella Chiaramonte ◽  
...  
Keyword(s):  
Epigenetic Modification ◽  
Lung Parenchyma ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Differential Modulation ◽  
Cystic Lung ◽  
Epidermal Growth ◽  
And Migration ◽  
Egfr Antibody

Matrix metalloproteinase (MMP) dysregulation is implicated in several diseases, given their involvement in extracellular matrix degradation and cell motility. In lymphangioleiomyomatosis (LAM), a pulmonary rare disease, MMP-2 and MMP-9 have been detected at high levels in serum and urine. LAM cells, characterized by a mutation in the tuberous sclerosis complex (TSC)1 or TSC2, promote cystic lung destruction. The role of MMPs in invasive and destructive LAM cell capability has not yet been fully understood. We evaluated MMP-2 and MMP-7 expression, secretion, and activity in primary LAM/TSC cells that bear a TSC2 germline mutation and an epigenetic modification and depend on epidermal growth factor (EGF) for survival. 5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody. Both drugs reduced MMP-2 and MMP-7 secretion and activity during wound healing and decreased their expression in lung nodules of a LAM mouse model. In LAM/TSC cells, MMP-2 and MMP-7 are dependent on tuberin expression, cellular adhesion, and migration. MMPs appears sensitive to rapamycin and anti-EGFR antibody only during cellular migration. Our data indicate a complex and differential modulation of MMP-2 and MMP-7 in LAM/TSC cells, likely critical for lung parenchyma remodeling during LAM progression.

scholarly journals Effects of a New Bioceramic Material on Human Apical Papilla Cells

2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mineral Trioxide Aggregate ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cellular Viability ◽  
Migration Rates ◽  
Apical Papilla ◽  
And Migration ◽  
Proliferation And Migration

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.

scholarly journals The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

2011 ◽  
Vol 22 (17) ◽  
pp. 3032-3040 ◽  
Author(s):  
Aichi Msaki ◽  
Ana M. Sánchez ◽  
Li Fang Koh ◽  
Benjamin Barré ◽  
Sonia Rocha ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cellular Migration ◽  
Negative Regulator ◽  
Drug Induced ◽  
Conserved Residues ◽  
Cellular Processes ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela−/−mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration.

Vitronectin acts as a key regulator of adhesion and migration in umbilical cord-derived MSCs under different stress conditions

2021 ◽  
Author(s):  
Malancha Ta ◽  
Ankita Sen
Keyword(s):  
Cellular Therapy ◽  
Cellular Adhesion ◽  
Stress Conditions ◽  
Cellular Migration ◽  
Serum Starvation ◽  
Erk Pathway ◽  
Stress Fibre ◽  
Spread Area ◽  
And Migration ◽  
Cell Spread

Mesenchymal stem cell (MSC)-based cellular therapy gets compromised as adverse microenvironmental conditions like nutrient deprivation, ischemia, hypoxia affect migration and engraftment, in addition to viability, of MSCs at the target site post transplantation. To improve the treatment efficacy, it is critical to identify factors involved in regulating migration and adhesion of MSCs under such microenvironmental stress conditions. In our study, we observed that Wharton's jelly-MSCs (WJ-MSCs) exhibited increase in cell spread area and adhesion with reduction in cellular migration under serum starvation. The changes in adhesion and migration characteristics were accompanied by extensive stress fibre formation and altered ECM gene expression with notable induction in vitronectin (VTN) expression and reduction in MMP-1 expression. Molecular and phenotypic correlative studies advocated the possible role of VTN and not MMP-1, in regulating adhesion and migration of WJ-MSCs. NF-kb was found to be the positive regulator of VTN expression while ERK pathway regulated it negatively. Further investigation with inhibition of these signalling pathways or VTN knockdown studies under serum starvation established the correlation between increase in VTN expression and increased cellular adhesion with corresponding reduction in migration. VTN knockdown under serum starvation also led to reduction in actin stress fibre along with reversal in expression of several ECM genes. Additionally, VTN induction being absent in hypoxia-treated WJ-MSCs, the hypoxic cells showed no significant change in the adhesion and migration properties. However, when VTN expression was induced under hypoxia by ERK pathway inhibition, similar increase in cell spread area and adhesion was observed. Our study thus highlights VTN as a factor which is induced under serum starvation stress and possibly affects the adhesion and migration properties of WJ-MSCs.

scholarly journals A potential therapy for chordoma via antibody-dependent cell-mediated cytotoxicity employing NK or high-affinity NK cells in combination with cetuximab

2018 ◽  
Vol 128 (5) ◽  
pp. 1419-1427 ◽  
Author(s):  
Rika Fujii ◽  
Jeffrey Schlom ◽  
James W. Hodge
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Growth Factor Receptor ◽  
High Affinity ◽  
Dependent Cell ◽  
Epidermal Growth ◽  
First Time ◽  
Igg1 Isotype ◽  
Egfr Antibody

OBJECTIVEChordoma is a rare bone tumor derived from the notochord and is resistant to conventional therapies such as chemotherapy, radiotherapy, and targeting therapeutics. Expression of epidermal growth factor receptor (EGFR) in a large proportion of chordoma specimens indicates a potential target for therapeutic intervention. In this study the authors investigated the potential role of the anti-EGFR antibody cetuximab in immunotherapy for chordoma.METHODSSince cetuximab is a monoclonal antibody of the IgG1 isotype, it has the potential to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) employing natural killer (NK) cells as effectors. Polymorphisms in the CD16 allele expressed on NK cells have been shown to influence the degree of ADCC of tumor cells, with the high-affinity valine (V)/V allele being responsible for more lysis than the V/phenylalanine (F) or FF allele. Unfortunately, however, only approximately 10% of the population expresses the VV allele on NK cells. An NK cell line, NK-92, has now been engineered to endogenously express IL-2 and the high-affinity CD16 allele. These irradiated high-affinity (ha)NK cells were analyzed for lysis of chordoma cells with and without cetuximab, and the levels of lysis observed in ADCC were compared with those of NK cells from donors expressing the VV, VF, and FF alleles.RESULTSHere the authors demonstrate for the first time 1) that cetuximab in combination with NK cells can mediate ADCC of chordoma cells; 2) the influence of the NK CD16 polymorphism in cetuximab-mediated ADCC for chordoma cell lysis; 3) that engineered haNK cells—that is, cells transduced to express the CD16 V158 FcγRIIIa receptor—bind cetuximab with similar affinity to normal NK cells expressing the high-affinity VV allele; and 4) that irradiated haNK cells induce ADCC with cetuximab in chordoma cells.CONCLUSIONSThese studies provide rationale for the use of cetuximab in combination with irradiated haNK cells for therapy for chordoma.

scholarly journals Control of cellular motility by neuropilin-mediated physical interactions

2014 ◽  
Vol 5 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Xiaobo Li ◽  
Matthew W. Parker ◽  
Craig W. Vander Kooi
Keyword(s):  
Physiological Role ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cellular Motility ◽  
Tumor Cell Migration ◽  
Surface Receptors ◽  
Multistep Process ◽  
Physical Interactions ◽  
Adhesive Interactions

AbstractThe neuropilin (Nrp) family consists of multifunctional cell surface receptors with critical roles in a number of different cell and tissue types. A core aspect of Nrp function is in ligand-dependent cellular migration, where it controls the multistep process of cellular motility through integration of ligand binding and receptor signaling. At a molecular level, the role of Nrp in migration is intimately connected to the control of adhesive interactions and cytoskeletal reorganization. Here, we review the physiological role of Nrp in cellular adhesion and motility in the cardiovascular and nervous systems. We also discuss the emerging pathological role of Nrp in tumor cell migration and metastasis, providing motivation for continued efforts toward developing Nrp inhibitors.

scholarly journals PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juliane Obst ◽  
Hazel L. Hall-Roberts ◽  
Thomas B. Smith ◽  
Mira Kreuzer ◽  
Lorenza Magno ◽  
...  
Keyword(s):  
Calcium Release ◽  
Cell Function ◽  
Immune Cell ◽  
Induced Pluripotent Stem Cell ◽  
Myeloid Cell ◽  
Cellular Adhesion ◽  
Calcium Flux ◽  
Surface Receptors ◽  
And Migration

AbstractHuman genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.

scholarly journals Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

2018 ◽  
Vol 45 (3) ◽  
pp. 1172-1190 ◽  
Author(s):  
Qingdong Zhao ◽  
Mingxia Ye ◽  
Wen Yang ◽  
Min Wang ◽  
Mingxia Li ◽  
...  
Keyword(s):  
Mitochondrial Fission ◽  
Cellular Migration ◽  
Functional Study ◽  
Mitochondrial Apoptosis ◽  
Normal Endometrium ◽  
Endometrial Stromal Cells ◽  
Western Blots ◽  
Mitochondrial Functions ◽  
And Migration

Background/Aims: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. Methods: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1 was conducted via adenovirus over-expression. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The mitophagy activity were examined via western blots and immunofluorescence. Results: First, we found that Mst1 was significantly downregulated in the ectopic endometrium of endometriosis compared to the normal endometrium. However, the recovery of Mst1 function was closely associated with the inability of endometrial stromal cells (ESCs) to migrate and survive. A functional study indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation at Ser616 and repressed Parkin transcription activity via p53, leading to mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm. Moreover, Mst1-induced defective mitophagy evoked cellular oxidative stress, energy metabolism and calcium overload. Through excessive mitochondrial fission and aberrant mitophagy, Mst1 launched caspase 9-related mitochondrial apoptosis and abrogated F-actin/lamellipodium-dependent cellular migration. Notably, we also defined NR4A/miR181c as the upstream signal for Mst1 dysfunction in endometriosis. Conclusion: Collectively, our results comprehensively described the important role of the NR4A-miR181c-Mst1 pathway in endometriosis, which handled mitochondrial apoptosis and F-actin/ lamellipodium-based migration via the regulation of Drp1-related mitochondrial fission and Parkin-required mitophagy, with a potential application in endometriosis therapy by limiting ESCs migration and promoting apoptosis.

scholarly journals Analysis of expression of genes responsible for regulation of cellular proliferation and migration – microarray approach based on porcine oocyte model

2019 ◽  
Vol 7 (2) ◽  
pp. 48-57 ◽  
Author(s):  
Agata Chamier-Gliszczyńska ◽  
Sandra Kałużna ◽  
Katarzyna Stefańska ◽  
Piotr Celichowski ◽  
Paweł Antosik ◽  
...  
Keyword(s):  
In Vitro Maturation ◽  
Cellular Proliferation ◽  
Cellular Migration ◽  
Affymetrix Microarray ◽  
Expression Of Genes ◽  
Before And After ◽  
Porcine Oocyte ◽  
And Migration

AbstractThe formation of mammalian oocytes begins in the ovary during fetal development. The proper development of oocytes requires close communication with surrounding somatic cells, the substances they emit allow proper maturation of oocytes. Somatic cumulus (CC) cells and oocytes form cumulus-oocyte (COC) complexes.In this study, the Affymetrix microarray analysis was used to investigate changes in gene expression occurring in oocytes before and after in vitro maturation (IVM). The aim of the study was to examine oocyte genes involved in two ontological groups, “regulation of cell migration” and “regulation of cell proliferation” discovered by the microarray method.We found a reduced expression of all 28 genes tested in the ontological groups: ID2, VEGFA, BTG2, CCND2, EDNRA, TGFBR3, GJA, LAMA2, RTN4, CDK6, IHH, MAGED1, INSR, CD9, PTGES, TXNIP, ITGB1, SMAD4, MAP3K1, NOTCH2 , IGFBP7, KLF10, KIT, TPM1, PLD1, BTG3, CD47 and MITF. We chose the most regulated genes down the IVM culture, and pointed out those belonging to two ontological groups.Increased expression of the described genes before IVM maturation may indicate the important role of these genes in the process of ovum maturation. After the maturation process, the proteins produced by them did not play such an important role. In summary, the study provides us with many genes that can serve as molecular markers of oocyte processes associated with in vitro maturation. This knowledge can be used for detailed studies on the regulation of oocyte maturation processes.Running title: Genes regulating cellular migration and proliferation in porcine oocytes

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