Hyperglycemia reduces integrin subunits alpha v and alpha 5 on the surface of dermal fibroblasts contributing to deficient migration

Almeida, Maíra Estanislau Soares de; Monteiro, K. S.; Kato, Ellen Emi; Sampaio, Sandra Coccuzzo; Braga, Tárcio Teodoro; Câmara, Niels Olsen Saraiva; Lamers, Marcelo Lazzaron; Santos, Marinilce Fagundes dos

doi:10.1007/s11010-016-2780-4

Cited by 25 publications

(27 citation statements)

References 28 publications

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“…Moreover, integrin expression levels are sensitive to glucose level in different cell types. Hyperglycaemia may thus modify integrin expression and its intracellular signalling in β‐cell, comparable to that observed in endothelial cells (Roth et al., ) or fibroblast (Almeida et al., ).…”

Section: Ecm Adhesion and Diabetessupporting

confidence: 56%

Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions

Arous

Wehrle-Haller

2017

Biology of the Cell

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Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β-cells, and to recognise and revert the physiopathology of diabetes. Indeed, integrin-mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β-cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin-mediated cell-matrix adhesions and how they are affected during diabetes. To treat diabetes, a promising approach consists in replacing β-cells by transplantation. However, efficiency is low, because β-cells suffer of anoikis, due to enzymatic digestion of the pancreatic ECM, which affects the survival of insulin-secreting β-cells. The strategy of adding ECM components during transplantation, to reproduce the pancreatic microenvironment, is a challenging task, as many of the regulatory mechanisms that control ECM deposition and turnover are not sufficiently understood. A better comprehension of the impact of the ECM on the adhesion and integrin-dependent signalling in β-cells is primordial to improve the healthy state of islets to prevent the onset of diabetes as well as for enhancing the efficiency of the islet transplantation therapy.

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Section: Ecm Adhesion and Diabetessupporting

confidence: 56%

Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions

Arous

Wehrle-Haller

2017

Biology of the Cell

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“…Indeed, Varner et al [19] reported that cell behavior depends on the adhesion to FN and on ITGA5 subunit expression. Moreover, a recent study showed that the migration ability of dermal fibroblasts improved following their exposure to FN [27]. …”

Section: Discussionmentioning

confidence: 99%

Fibroblast paracrine TNF-α signaling elevates integrin A5 expression in idiopathic pulmonary fibrosis (IPF)

et al. 2017

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Inflammatory cytokines play a significant role in IPF pathology. However, the fibroblast itself is also believed to be the primary effector in IPF. We hypothesized that the fibroblasts themselves secrete pro-inflammatory cytokines that could propagate IPF by affecting normal neighboring cells. Thus, we explored the effects of IPF fibroblast derived media on normal fibroblast characteristics.MethodsPrimary IPF/normal tissue derived fibroblast cultures were established and their supernatants were collected (IPF/N-SN, respectively). These supernatants were added to normal fibroblasts. Cell death (caspase-3, western blot), proliferation, viability (WST-1), migration (scratch test) and cell detachment (crystal violet and fibronectin adhesion assays) were tested. 10 inflammatory cytokines were measured by ELISA-based quantitative array. Integrin α5 (ITGA5), pIκBα, p/total STAT3 levels were measured by western blot/IHC. TNF-α involvement was confirmed using Infliximab ®, anti-TNF-α mAb.ResultsThe IPF-SN facilitated fibroblast cell detachment and reduced cell migration (p < 0.05). Nevertheless, these effects were reversed when cells were seeded on fibronectin. The exposure to the IPF-SN also elevated ITGA5 levels, the fibronectin receptor, in addition to NFκB pathway activation (pIκBα↑ 150%, p < 0.05). In accordance, IPF derived fibroblasts were found to express higher ITGA5 than the normal cells (44%↑, p < 0.05). ITGA5 was also expressed in the fibroblastic foci.The IPF-SN contained high TNF-α levels (3-fold, p < 0.05), and Infliximab pretreatment successfully reversed all the above observations.ConclusionWe suggest a possible mechanism in which IPF fibroblast secreted TNF-α modifies neighboring fibroblast cell behavior.

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“…The selection of the pore size was based on previous literature studies which used this type of transwell system to evaluate fibroblast migration [14, 15]. It was also considered the characteristics of the fibroblast cell type, such as their size (10–15 um).…”

Section: Methodsmentioning

confidence: 99%

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

et al. 2017

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Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α2β1 integrin (VLA-2) and the laminin receptor very late antigen 6, α6β1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-017-1982-3) contains supplementary material, which is available to authorized users.

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Hyperglycemia reduces integrin subunits alpha v and alpha 5 on the surface of dermal fibroblasts contributing to deficient migration

Cited by 25 publications

References 28 publications

Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions

Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions

Fibroblast paracrine TNF-α signaling elevates integrin A5 expression in idiopathic pulmonary fibrosis (IPF)

Metallic nanoparticles reduce the migration of human fibroblasts in vitro

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