Increased expression of the coxsackie and adenovirus receptor downregulates αvβ3 and αvβ5 integrin expression and reduces cell adhesion and migration

Majhen, Dragomira; Stojanović, Nikolina; Špeljko, Tea; Brozović, Anamaria; Zan, Tihana De; Osmak, Maja; Ambriović-Ristov, Andreja

doi:10.1016/j.lfs.2011.06.009

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…Various subtypes of integrins mediate cell adhesion in a cell type-specific manner [37]. In cardiac fibroblasts, previous studies demonstrated the involvement of β1 integrin in cell adhesion [13].…”

Section: Discussionmentioning

confidence: 99%

β3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse

et al. 2012

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The adhesion receptor β3 integrin regulates diverse cellular functions in various tissues. As β3 integrin has been implicated in extracellular matrix (ECM) remodeling, we sought to explore the role of β3 integrin in cardiac fibrosis by using wild type (WT) and β3 integrin null (β3−/−) mice for in vivo pressure overload (PO) and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, β3−/− mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC) showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from β3−/− mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1) expression in early time points of PO. To test if the observed impairment of ECM accumulation in β3−/− mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and β3−/− mice for adhesion to ECM proteins, cell spreading, proliferation, and migration in response to platelet derived growth factor-BB (PDGF, a growth factor known to promote fibrosis) stimulation. Our results showed that β3−/− cardiac fibroblasts exhibited a significant reduction in cell-matrix adhesion, cell spreading, proliferation and migration. In addition, the activation of PDGF receptor associated tyrosine kinase and non-receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in β3−/− cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F) resulted in reduced accumulation of fibronectin. These results indicate that β3 integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in PO-induced cardiac fibrosis.

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Section: Discussionmentioning

confidence: 99%

β3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse

et al. 2012

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“…This fact is based on the ability of CAR to bind proteins, such as ZO1, b-catenin and MUPP1 (Cohen et al 2001, Walters et al 2002, Coyne et al 2004. As a consequence of its connection to cellular adhesion, CAR has also been associated with carcinogenesis -exhibiting mainly tumour-suppressive activity (Kim et al 2003, Pong et al 2003, Fan et al 2009, Wu et al 2010, Majhen et al 2011.…”

Section: Introductionmentioning

confidence: 99%

CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions

Krivega¹,

Geens²,

Velde³

2014

Reproduction

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Coxsackie virus and adenovirus receptor, CXADR (CAR), is present during embryogenesis and is involved in tissue regeneration, cancer and intercellular adhesion. We investigated the expression of CAR in human preimplantation embryos and embryonic stem cells (hESC) to identify its role in early embryogenesis and differentiation. CAR protein was ubiquitously present during preimplantation development. It was localised in the nucleus of uncommitted cells, from the cleavage stage up to the precursor epiblast, and corresponded with the presence of soluble CXADR3/7 splice variant. CAR was displayed on the membrane, involving in the formation of tight junction at compaction and blastocyst stages in both outer and inner cells, and CAR corresponded with the full-length CAR-containing transmembrane domain. In trophectodermal cells of hatched blastocysts, CAR was reduced in the membrane and concentrated in the nucleus, which correlated with the switch in RNA expression to the CXADR4/7 and CXADR2/7 splice variants. The cells in the outer layer of hESC colonies contained CAR on the membrane and all the cells of the colony had CAR in the nucleus, corresponding with the transmembrane CXADR and CXADR4/7. Upon differentiation of hESC into cells representing the three germ layers and trophoblast lineage, the expression of CXADR was downregulated. We concluded that CXADR is differentially expressed during human preimplantation development. We described various CAR expressions: i) soluble CXADR marking undifferentiated blastomeres; ii) transmembrane CAR related with epithelial-like cell types, such as the trophectoderm (TE) and the outer layer of hESC colonies; and iii) soluble CAR present in TE nuclei after hatching. The functions of these distinct forms remain to be elucidated.

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“…More importantly, integrin b3 is known to be a receptor or co-receptor for many viruses, such as Rotavirus [27][28][29][30], Hantavirus [31][32][33], and Foot-and-mouth disease virus [34,35]. It also plays a key role in infection processes of Adenovirus [36,37], West Nile Virus [32], Human immunodeficiency virus [38,39], Human Parecho virus [40][41][42], and Herpes simplex virus type 1 [43][44][45]. Furthermore, previous studies from our laboratory have shown that integrin b3 is up-regulated in endothelial cells post CSFV infection (post CSFV infection = p.i.)…”

Section: Introductionmentioning

confidence: 99%

Integrin β3 Is Required in Infection and Proliferation of Classical Swine Fever Virus

Wang

Liang

et al. 2014

PLoS ONE

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Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry. Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses. However, the role of integrin β3 in CSFV infection is unknown. Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells. Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation. Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells. ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level. CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively. These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.

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Increased expression of the coxsackie and adenovirus receptor downregulates αvβ3 and αvβ5 integrin expression and reduces cell adhesion and migration

Cited by 10 publications

References 38 publications

β3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse

β3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse

CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions

Integrin β3 Is Required in Infection and Proliferation of Classical Swine Fever Virus

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