Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells

Mariko, Boubacar; Ghandour, Zeinab; Raveaud, Stéphanie; Quentin, Mickaël; Usson, Yves; Verdetti, Jean; Huber, Philippe; Kielty, Cay M.; Faury, Gilles

doi:10.1152/ajpcell.00377.2009

Cited by 35 publications

(24 citation statements)

References 74 publications

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“…Of note, α v β 3 integrin is a crucial angiogenesis regulator [56] and fibrillin-1 has been reported to induce α v β 3 integrin-mediated signaling in human endothelial cells [57]. Thus, CYC treatment might exert a proangiogenic effect by maintaining endothelial α v β 3 integrin expression and fibrillin-1 deposition at normal levels.…”

Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

et al. 2015

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In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial cell-matrix interactions. Our objective was to evaluate in vitro the effects of sera from treatment-naïve or CYC-treated SSc patients on dermal blood microvascular endothelial cell (dMVEC) angiogenesis, migration, proliferation and apoptosis. dMVECs were challenged with sera from 21 SSc patients, treatment-naïve (n = 8) or under CYC treatment (n = 13), and 8 healthy controls. Capillary morphogenesis on Geltrex matrix was significantly reduced upon challenge with sera from naïve SSc patients compared with healthy controls. When dMVECs were challenged with sera from CYC-treated SSc patients, their angiogenic capacity was comparable to that of cells treated with healthy sera. Wound healing capacity and chemotaxis in Boyden chamber were both significantly decreased in the presence either of naïve or CYC-treated SSc sera compared with healthy sera. WST-1 assay revealed that cell proliferation was significantly decreased in dMVECs challenged with sera from naïve SSc patients compared with healthy sera. Conversely, dMVEC proliferation was not impaired in the presence of sera from CYC-treated SSc patients. Accordingly, the percentage of TUNEL-positive apoptotic dMVECs was significantly higher in the presence of sera from naïve SSc patients than healthy controls, while CYC-treated SSc sera did not induce dMVEC apoptosis. Levels of the angiostatic mediators endostatin, pentraxin 3, angiostatin and matrix metalloproteinase-12 were all significantly elevated in sera from naïve SSc patients compared with sera from both healthy controls and CYC-treated SSc patients. In SSc, CYC treatment might boost angiogenesis and consequently improve peripheral microangiopathy through the normalization of the endothelial cell-matrix interactions, reduction of endothelial cell apoptosis and rebalance of dysregulated angiostatic factors.

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Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

et al. 2015

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“…22 Both integrins are known to propagate migration or proliferation not only of mesangial cells, 22 but also of other cell types adhering to fibrillin-1, such as endothelial cells. 23 Thus, the increased migratory and proliferative activity of mesangial cells lacking a8 integrin argues for a counter regulatory effect of a8 integrin activity, which reduces wild type mesangial cell migration and basal proliferation rates. Previous studies employing a8 integrin-deficient mesangial cells revealed equal amounts of cell surface expression of av and a5 integrins when compared with wild type mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells

Marek

Volkert

Hilgers

et al. 2014

Cell Adhesion & Migration

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Fibrillin-1 is a microfibrillar extracellular matrix protein that was described to be a ligand for α8 integrin. α8 integrin is a matrix receptor specifically expressed in mesangial and smooth muscle cells of the kidney. In previous studies we detected glomerular expression of fibrillin-1. Moreover, fibrillin-1 promoted adhesion, migration, and proliferation of mesangial cells. We hypothesized that fibrillin-1 and α8 integrin might interact in the glomerulus, and thus, regulate mesangial cell properties. Our studies showed that fibrillin-1 and α8 integrin colocalize in the glomerular mesangium. Induction of experimental glomerulonephritis led to an increase of both fibrillin-1 and α8 integrin expression. In vitro studies revealed that mesangial cells deficient for α8 integrin adhere weaker to fibrillin-1 and migrate more easily on fibrillin-1 than wild-type mesangial cells. Baseline proliferation on fibrillin-1 is higher in α8 integrin-deficient mesangial cells, but the induction of proliferation is not different in α8 integrin-deficient and wild-type mesangial cells. We conclude that fibrillin-1 and α8 integrin interact, and thus, regulate mesangial cell adhesion and migration. The concomitant induction of both fibrillin-1 and α8 integrin in a self-limited model of glomerular injury points to a protective role of the interaction of fibrillin-1 with α8 integrin in the glomerulus resulting in reduced damage of the glomerular tuft as a consequence of firm adhesion of mesangial cells.

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“…Fibrillin-1 contains an Arg-GlyAsp (RGD) sequence within the TB4 domain which interacts with cell surface integrins (Bax et al 2007;Jovanovic et al 2007;McGowan et al 2008). These interactions have important roles to play in the microfibrillar assembly process and in cellular adhesion, aVb3, a5b1 and aVb6 integrins all interact with fibrillin-1 and display high (Kd 40 nM), moderate (Kd 450 nM) and low (Kd [ 1 lM) binding affinities, respectively (Jovanovic et al 2008), avb3 integrin regulates microfibril assembly in periodontal ligament cells (Tsuruga et al 2009), and along with a5b1 integrin has a role in the activation of human umbilical vein endothelial cells (Mariko et al 2010) and lung fibroblasts (McGowan et al 2008), mediating cell signaling, proliferation, cell migration and in the provision of focal adhesions. These comments are consistent with fibrillin-1 fibrils which were observed in the present study, attached to cells in the posterior longitudinal ligament and outer annulus fibrosus and with regulatory roles in mechanotransductive processes which orchestrate extracellular matrix development and remodelling and maintenance of a homeostasic balance in extracellular matrix components.…”

Section: Discussionmentioning

confidence: 99%

Colocalization in vivo and association in vitro of perlecan and elastin

Hayes

Lord

Smith

et al. 2011

Histochem Cell Biol

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We have colocalized elastin and fibrillin-1 with perlecan in extracellular matrix of tensional and weight-bearing connective tissues. Elastin and fibrillin-1 were identified as prominent components of paraspinal blood vessels, and posterior longitudinal ligament in the human fetal spine and outer annulus fibrosus of the fetal intervertebral disc. We also colocalized perlecan with a synovial elastic basal lamina, where the attached synovial cells were observed to produce perlecan. Elastin, fibrillin-1 and perlecan were co-localized in the intima and media of small blood vessels in the synovium and in human fetal paraspinal blood vessels. Elastic fibers were observed at the insertion point of the anterior cruciate ligament to bone in the ovine stifle joint where they colocalized with perlecan. Elastin has not previously been reported to be spatially associated with perlecan in these tissues. Interactions between the tropoelastin and perlecan heparan sulfate chains were demonstrated using quartz crystal microbalance with dissipation solid phase binding studies. Electrostatic interactions through the heparan sulfate chains of perlecan and core protein mediated the interactions with tropoelastin, and were both important in the coacervation of tropoelastin and deposition of elastin onto perlecan immobilized on the chip surface. This may help us to understand the interactions which are expected to occur in vivo between the tropoelastin and perlecan to facilitate the deposition of elastin and formation of elastic microfibrils in situ and would be consistent with the observed distributions of these components in a number of connective tissues.

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Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells

Abstract: Kielty C, Faury G. Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells.

Cited by 35 publications

References 74 publications

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells

Colocalization in vivo and association in vitro of perlecan and elastin

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