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Search results for: CD49d

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#32734582   2020/07/30 To Up

NSun2 regulates aneurysm formation by promoting autotaxin expression and T cell recruitment.

Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell infiltration and aggravated by hyperhomocysteinemia (HHcy). It is unknown whether the homocysteine (Hcy)-activated RNA methyltransferase NOP2/Sun domain family member 2 (NSun2) is associated with AAA. Here, we found that NSun2 deficiency significantly attenuated elastase-induced and HHcy-aggravated murine AAA with decreased T cell infiltration in the vessel walls. T cell labeling and adoptive transfer experiments confirmed that NSun2 deficiency inhibited the chemotaxis of vessels to T cells. RNA sequencing of endothelial cells showed that Hcy induced the accumulation of various metabolic enzymes of the phospholipid PC-LPC-LPA metabolic pathway, especially autotaxin (ATX). In the elastase-induced mouse model of AAA, ATX was specifically expressed in the endothelium and the plasma ATX concentration was upregulated and even higher in the HHcy group, which were decreased dramatically by NSun2 knockdown. In vitro Transwell experiments showed that ATX dose-dependently promoted T cell migration. HHcy may upregulate endothelial ATX expression and secretion and in turn recruit T cells into the vessel walls to induce vascular inflammation and consequently accelerate the pathogenesis of AAA. Mechanistically, secreted ATX interacted with T cells by binding to integrin α4, which subsequently activated downstream FAK/Src-RhoA signaling pathways and then induced T cell chemokinesis and adhesion. ATX overexpression in the vessel walls reversed the inhibited development of AAA in the NSun2-deficient mice. Therefore, NSun2 mediates the development of HHcy-aggravated AAA primarily by increasing endothelial ATX expression, secretion and T cell migration, which is a novel mechanism for HHcy-aggravated vascular inflammation and pathogenesis of AAA.
Yutong Miao, Yang Zhao, Lulu Han, Xiaolong Ma, Jiacheng Deng, Juan Yang, Silin Lü, Fangyu Shao, Wei Kong, Wengong Wang, Qingbo Xu, Xian Wang, Juan Feng

2546 related Products with: NSun2 regulates aneurysm formation by promoting autotaxin expression and T cell recruitment.

100.00 ug15ml25 mg100 ug100 μg 1KG

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#32706337   2020/07/24 To Up

FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

In this study, human adipose stem cells were isolated from subcutaneous fat in the thigh (htASCs), abdomen (haASCs) and breast (hbASCs). Flow cytometry was used to detect cell surface markers, and an enzyme-linked immunosorbent assay was used to detect paracrine activity. Paracrine gene expression in the three cell types was examined using real-time qPCR, and adipogenic ability was assessed using Oil Red O staining. RNA from third-passage haASCs and hbASCs was sequenced. The results showed that the differentiation potential marker markers CD49d and CD54 were similar across hbASCs from 10 subjects. The hbASCs showed higher colony forming ability and expression of fibroblast growth factor-2, tissue inhibitor of metalloproteinase-1 and stromal cell derived factor-1 than htASCs and haASCs. Stimulating hbASCs with FGF2 promoted adipogenic differentiation, while treating the cells with the PI3K inhibitor LY294002 inhibited differentiation. These results suggest that the PI3K/Akt signaling pathway can promote proliferation and adipogenic differentiation of adipose stem cells, and that activation of this pathway by FGF2 may explain why hbASCs show greater proliferation and adipogenic differentiation than haASCs and htASCs.
Guan-Ming Lu, Yong-Xian Rong, Zhi-Jie Liang, Dong-Lin Hunag, Fang-Xiao Wu, Yan-Fei Ma, Zhi-Zhai Luo, Xin-Heng Liu, Steven Mo, Hong-Mian Li

1297 related Products with: FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

5 x 50 ug50 ug0.1 mg1 mg10 ug24 wells1200 1.5x10(6) cells 100ul

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#32696438   2020/07/21 To Up

Conversion of Neural Stem Cells into Functional Neuron-Like Cells by MicroRNA-218: Differential Expression of Functionality Genes.

Conversion of mesenchymal stem cells (MSC) into neuron-like cells (NLC) is a feasible cell therapy strategy for replacing lost neurons in neuronal disorders. In this study, adipose-derived MSC (ADMSC) were converted into neural stem cells (NSC) via neurosphere. The resulting NSC were then differentiated into NLC by transduction with microRNA-218, using a lentiviral vector. ADMSC, NSC, and NLC were first characterized by flow cytometry, RT-PCR, and immunocytochemistry. The functionality of the NLC was evaluated by qRT-PCR and patch clamp recording. Immunophenotyping of ADMSC showed their immunoreactivity to MSC markers CD90, CD73, CD105, and CD49d, but not to CD31 and CD45. RT-PCR results demonstrated the expression of nestin, neurogenin, neurod1, neurofilament light, and GAP43 genes in NSC while NLC expressed synaptophysin, neurofilament heavy, and GAP43. In addition, NSC morphology changed into multipolar with long processes after transduction with miR-218. Moreover, using qRT-PCR, the expression levels of miR-218 and functionality genes CACNA1C, SNAP25, KCNH1, KCNMA1, and SCN9A were significantly increased in NLC, compared with NSC, and ADMSC at 3 weeks and 5 months post-transduction. Furthermore, the generated NLC expressed significantly higher protein levels of neurofilament heavy polypeptide (NFh) and enolase 2 (Eno2) neuronal markers, compared with ADMSC and NSC. Finally, action potentials were successfully recorded by the generated NLC, using patch clamp. In summary, ADMSC-derived NSC differentiated into functional NLC by transduction with miR-218. The generated NLC expressed functional SNAP25, CACNA1C, KCNH1, KCNMA1, and SCN9A and produced an action potential, which provides useful insights into the generation of functional neuronal cells.
Wissam Khalil, Taki Tiraihi, Masoud Soleimani, Nafiseh Baheiraei, Kazem Zibara

1137 related Products with: Conversion of Neural Stem Cells into Functional Neuron-Like Cells by MicroRNA-218: Differential Expression of Functionality Genes.

11 x 10^6 cells/vial1 mg10 ug5 x 10A5 cells/vial100 ug/vial210ml2.00 flask

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#32680928   2020/07/17 To Up

Molecular Imaging of Very Late Antigen-4 (VLA-4) in Acute Lung Injury.

Inflammation plays a central role in the pathogenesis of acute lung injury (ALI) during both the acute pneumonitis stage and the progression into the chronic fibroproliferative phase, leading to pulmonary fibrosis. Currently, there is an unmet clinical and research need for non-invasive approaches to monitor lung inflammation through targeting immunoregulatory pathways contributing to ALI pathogenesis. In this study, we evaluated the role of targeted imaging of very late antigen-4 (VLA-4), as a key integrin mediating the adhesion and recruitment of immune cells to inflamed tissues, in quantifying lung inflammation in a mouse model of lipopolysaccharide-induced ALI. ALI was induced by a single intra-tracheal administration of lipopolysaccharide (10, 20 or 40 µg per mouse) in C57BL/6J mice. Control mice were intra-tracheally instilled with sterile phosphate-buffered saline. VLA-4 targeted PET/CT was performed 24 hours after intravenous injection of a copper-64 (Cu) labeled high-affinity peptidomimetic ligand, Cu-CB-TE1A1P-PEG4-LLP2A (Cu-LLP2A), at day 2 after the induction of ALI. Ex vivo biodistribution of Cu-LLP2A was determined by γ-counting of harvested organs. The severity of lung inflammation was assessed histologically and by measuring the expression of inflammatory markers in the lung tissue lysates using reverse transcription quantitative polymerase chain reaction. Intra-tracheal lipopolysaccharide instillation led to an acute inflammatory response in the lungs, characterized by increased expression of multiple inflammatory markers and infiltration of myeloid cells, along with a significant and specific increase in Cu-LLP2A uptake, predominantly in a peribronchial distribution. There was a strong correlation between the lipopolysaccharide dose and Cu-LLP2A uptake, as quantified by in vivo PET (R=0.69, P<0.01). Expression levels of both subunits of VLA-4, i.e., integrins α4 and β1, significantly correlated with the expression of multiple inflammatory markers, including tumor necrosis factor-α, interleukin-1β and nitric oxide synthase-2, highlighting the potential of VLA-4 as a surrogate marker of acute lung inflammation. Notably, in vivo Cu-LLP2A uptake significantly correlated with the expression of multiple inflammatory markers and VLA-4. Our study demonstrates the feasibility of molecular imaging of VLA-4, as a mechanistically-relevant target in ALI, and the accuracy of VLA-4 targeted PET in quantification of ongoing lung inflammation in a murine model.
Joseph Haddad, Joseph D Latoche, Shubhanchi Nigam, Michael C Bellavia, Kathryn E Day, Qin Zhu, Wilson Barry Edwards, Carolyn J Anderson, Sina Tavakoli

2916 related Products with: Molecular Imaging of Very Late Antigen-4 (VLA-4) in Acute Lung Injury.

1mg0.1ml 5 G5mg 1 G4/120 Packing /sleeve/bo

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#32668403   2020/07/01 To Up

Integrins and OPN Localize to Adhesion Complexes during Placentation in Sheep.

Integrins and OPN are potential mediators of blastocyst attachment to the endometrium to initiate implantation. The goals were to examine the temporal/spatial pattern of expression of integrins at the endometrial-placental interface of sheep encompassing Days 9 through 80 of gestation, and determine if OPN co-localizes with integrins. Results show: (1) αv, α4, β1, β3 and β5 integrins at the apical surface of endometrial luminal epithelium (LE) from Days 11 through 16 of pregnancy that indicates a role for these integrins during implantation; (2) large, intermittent aggregates of αv, α4, α5, β1 and β5 integrins at the endometrial-placental interface from Days 20 through 55, suggesting adaptation to a localized tissue remodeling stage of placentation; and (3) integrin adhesion complexes (IACs) containing αv, α4, α5, β1 and β5 integrins precisely distribute at the apical surfaces of apposed endometrial LE and chorion along expanses of the interplacentomal endometrial-placental interface between Days 60 and 80 of gestation, suggesting engagement of these integrins with the ECM to stabilize adhesion between endometrial LE and chorion in response to the increasing mechanical stress on this interface by the increasing size of the fetus and volumes of fetal fluids. An advancement is the clear co-localization of OPN and integrins at the endometrial placental interface throughout gestation in sheep. The comprehensive nature of these results provide evidence that integrins potentially interact with OPN to play key roles in the mechanisms required for implantation and placentation throughout pregnancy in sheep, and have implications concerning implantation and placentation in other species.
Heewon Seo, James W Frank, Robert C Burghardt, Fuller W Bazer, Gregory A Johnson

2624 related Products with: Integrins and OPN Localize to Adhesion Complexes during Placentation in Sheep.

1 kit100 mg96 wells50100 96T0.1 ml101 mg100

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#32628938   2020/07/03 To Up

Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis.

Endocardium is critically important for proper function of the cardiovascular system. Not only does endocardium connect the heart to blood vasculature, it also plays an important role in heart morphogenesis, valve formation, and ventricular trabeculation. The extracellular protein Fibronectin (Fn1) promotes endocardial differentiation, but the signaling pathways downstream of Fn1 that regulate endocardial development are not understood. Here, we analyzed the role of the Fibronectin receptors Integrin alpha5 (Itga5) and Integrin alpha4 (Itga4) in zebrafish heart development. We show that itga5 mRNA is expressed in both endocardium and myocardium during early stages of heart development. Through analysis of both itga5 single mutants and itga4;itga5 double mutants, we show that loss of both itga5 and itga4 results in enhanced defects in endocardial differentiation and morphogenesis compared to loss of itga5 alone. Loss of both itga5 and itga4 results in cardia bifida and severe myocardial morphology defects. Finally, we find that loss of itga5 and itga4 results in abnormally narrow anterior endodermal sheet morphology. Together, our results support a model in which Itga5 and Itga4 cooperate to promote endocardial differentiation, medial migration of endocardial and myocardial cells, and morphogenesis of anterior endoderm.
Jennifer A Schumacher, Zoë A Wright, Mackenzie Owen, Nina O Bredemeier, Saulius Sumanas

1375 related Products with: Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis.

100ug Lyophilized200 100 mg100ug Lyophilized100ug10 mg100ul100ug100ug Lyophilized 100ul10 mg100ug Lyophilized

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#32616529   2020/07/02 To Up

CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment.
Julia C Gutjahr, Elisabeth Bayer, Xiaobing Yu, Julia M Laufer, Jan P Höpner, Suzana Tesanovic, Andrea Härzschel, Georg Auer, Tanja Rieß, Astrid Salmhofer, Eva Szenes, Theresa Haslauer, Valerie Durand-Onayli, Andrea Ramspacher, Sandra P Pennisi, Marc Artinger, Nadja Zaborsky, Alexandre Chigaev, Fritz Aberger, Daniel Neureiter, Lisa Pleyer, Daniel F Legler, Veronique Orian-Rousseau, Richard Greil, Tanja N Hartmann

1234 related Products with: CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.

1 mg100.00 ug5 x 50 Pieces/case 96tests2.5 g96T25 50 Pieces/case100 extractions

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#32572848   2020/06/23 To Up

Screening of integrins localized on the surface of human epidermal melanocytes.

In vivo, melanocytes occupy three-dimensional (3D) space. Nevertheless, most experiments involving melanocytes are performed in a two-dimensional microenvironment, resulting in difficulty obtaining accurate results. Therefore, it is necessary to construct an artificial in vivo-like 3D microenvironment. Here, as a step towards engineering a precisely defined acellular 3D microenvironment supporting the maintenance of human epidermal melanocytes (HEMs), we examined the types of integrin heterodimers that are expressed transcriptionally, translationally, and functionally in HEMs. Real-time PCR and fluorescent immunoassay analyses were used to elucidate the expression of integrin α and β subunit genes at the transcriptional and translational levels, respectively. The functionality of the presumed integrin heterodimers was confirmed using attachment and antibody-inhibition assays. Among the genes encoding 12 integrin subunits (α, α, α, α, α, α, α, α, β, β, β, and β) showing significantly higher transcription levels, proteins translated from the integrin α, α, α, β, β, and β subunit genes were detected on the surface of HEMs. These HEMs showed significantly increased adhesion to collagen I, fibronectin, laminin, and vitronectin, and functional blockade of the integrin α subunits significantly inhibited adhesion to collagen I, fibronectin, and laminin. In addition, there was no significant inhibition of the adhesion to fibronectin or vitronectin in HEMs with functional blockade of the integrin α, α, or α subunits. These results indicate that the active integrin αβ heterodimer and the inactive integrin α, α, α, β, and β subunits are all localized on the surface of HEMs.
Seong Jae Kim, Min Seong Kim, Hye Jin Park, Hyun Lee, Jung Im Yun, Hye Won Lim, Seung Tae Lee

2596 related Products with: Screening of integrins localized on the surface of human epidermal melanocytes.

5 G100 µg0.25 100ul50 ug0.1 mg1mg1 kit(96 Wells)50 ug2 100.1 mg

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#32571815   2020/06/22 To Up

Modulation of monocyte activation and function during direct antiviral agents treatment in HIV coinfected patients.

The activation phenotype and functional changes in monocyte subsets during HCV elimination in HIV/HCV-coinfected patients were evaluated. 22 HIV/HCV-coinfected patients on suppressive combination antiretroviral treatment (cART) achieving HCV elimination after direct-acting antivirals (DAAs) therapy and 10 HIV-monoinfected patients were included. Activation phenotype (10 markers) and polyfunctionality (intracellular IL1α, IL1β, IL6, IL8, TNFα and IL10 production) in three monocyte subsets (classical, intermediate and nonclassical) were evaluated by flow cytometry before and at the end of treatment. Cell-associated HIV-DNA levels were assayed by droplet digital PCR. After HCV clearance there was a significant increase in classical monocytes and a decrease in intermediate and nonclassical monocytes levels. The activation markers, CD49d, CD40, CX3CR1, decreased after treatment in the monocyte subsets reaching the levels of HIV-monoinfected patients. After LPS stimulation, although polyfunctionality significantly decreased in intermediate and nonclassical monocytes, some combinations such as IL1α-IL1β-IL6+IL8-TNFα-IL10- were remarkably increased at the end of treatment compared to the control group. Cell-associated HIV-DNA levels correlated with activation markers before but not after treatment. HCV clearance after DAAs treatment in patients on cART exerts an anti-inflammatory profile in monocyte subsets, activation phenotypes and polyfunctionality. However, there is not a complete normalization compared with HIV-monoinfected patients.
Rebeca S De Pablo-Bernal, M Reyes Jimenez-Leon, Laura Tarancon-Diez, Alicia Gutierrez-Valencia, Ana Serna-Gallego, Maria Trujillo-Rodriguez, Ana I Alvarez-Rios, Yusnelkis Milanes-Guisado, Nuria Espinosa, Cristina Roca-Oporto, Pompeyo Viciana, Luis F Lopez-Cortes, Ezequiel Ruiz-Mateos

2210 related Products with: Modulation of monocyte activation and function during direct antiviral agents treatment in HIV coinfected patients.

0.1ml48 samples100ug25 Bags/Unit100ug100μg2 mg100 ug100μg100 μg1 Set

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#32570252   2020/06/22 To Up

Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More.

Treatment of inflammatory bowel diseases (IBD) has tremendously improved during the last 20 years; however, a substantial fraction of patients does not respond to available therapies or lose response, and new strategies are needed.
Benjamin Misselwitz, Pascal Juillerat, Michael Christian Sulz, Britta Siegmund, Stephan Brand,

1341 related Products with: Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More.

1 mg10 ug96 tests1x10e7 cells96 tests100 µg5ug100

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