Dataset Information

Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells.

ABSTRACT: Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal-3 added to the culture medium. This association was reduced with a β-galactoside LacdiNAc (GalNAcβ1,4GlcNAc), a selective ligand of Gal-3, which binds to the carbohydrate recognition domain (CRD) in the Gal-3 molecule. This ligand was also able to detach Gal-3 newly associated with cells but not Gal-3 naturally present on cells. In addition, Gal-3 preadsorbed on plastic surfaces acted as an adhesion ligand for both cell types, and the cell adhesion was resistant to blocking with LacdiNAc. This result suggests that the adhesion was mediated by a binding site different from the CRD. The blocking of integrin adhesion receptors on cells with specific antibodies revealed that the cell adhesion to the preadsorbed Gal-3 was mediated, at least partially, by β1 and αV integrins-namely α5β1, αVβ3, and αVβ1 integrins.

SUBMITTER: Sedlar A

PROVIDER: S-EPMC8152275 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells.

Sedlář Antonín A Trávníčková Martina M Bojarová Pavla P Vlachová Miluše M Slámová Kristýna K Křen Vladimír V Bačáková Lucie L

International journal of molecular sciences 20210513 10

Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal ...[more]

PMID: 34067978

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Project description:BackgroundAcquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization.Methodology/principal findingsQuantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts.ConclusionsDecellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature.

Project description:Endotoxemia remains a major cause of mortality in the intensive care unit, but the therapeutic strategy is still lacking. Mesenchymal stem cell (MSC) was reported with a tissue-oriented differentiation ability and an excellent immunoregulatory capacity. However, the immunity signaling pathways that govern MSC modulation effect are not completely understood. In our current study, MSCs (2.5 × 105 /ml) were obtained and stimulated with IFN-γ (20 ng/ml) for 72 h. Gal-9 expression on MSCs was measured by ELISA, RT-PCR, flow cytometry, and immunofluorescence, respectively. Experimental endotoxemia was induced by LPS injection (10 mg/kg, i. p.) followed by the treatment with Gal-9 high-expressing MSCs, unmodified MSCs, and Gal-9 blocking MSCs. Therapeutic effects of MSCs were assessed by monitoring murine sepsis score, survival rate, splenocyte proportion rate, inflammatory mediator levels, and pathological manifestations. The results showed that Gal-9 expressed in MSCs, and this expression was increased in a dose-dependent manner after pre-stimulating with IFN-γ. Adoptive transfer of Gal-9 high-expressing MSCs into modeling mice significantly alleviated endotoxemia symptoms and multi-organ pathological damages. Splenocyte analysis indicated that Gal-9 high-expressing MSCs could promote macrophage polarization to M2-subtype and boost Treg generation. Moreover, there were also attenuated pro-inflammatory mediator expressions (TNF-α, IL-1β, IFN-γ, and iNOS), and increased anti-inflammatory mediator expressions (T-SOD and IL-35) in the sera and damaged organ homogenates. Additionally, we found a higher expression of Gal-9 in liver, lung, and kidney homogenate. Taken together, this study reveals that the optimized immunoregulatory effect of MSCs is strongly correlated with Gal-9 high expression, which provides a novel idea for the investigation of MSC immunomodulatory mechanisms and offers a potential strategy for the treatment of endotoxemia in clinical settings.

Dataset Information

Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells.

Publications

Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells.

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