Inflammatory cytokines stimulate vascular smooth muscle cells locomotion and growth by enhancing α5β1 integrin expression and function

Barillari, Giovanni; Albonici, Loredana; Incerpi, Sandra; Bogetto, Laura; Pistritto, Giuseppa; Volpi, Antonio; Ensoli, Barbara; Manzari, Vittorio

doi:10.1016/s0021-9150(00)00506-2

Cited by 64 publications

(53 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, we envision that the physical and functional interactions of these proteins are essential not only in cultured cells but also in vivo in various pathologic processes, particularly in the vasculature. Notably, up-regulation of PDGFR signaling function (29) and increased expression of the ␣5␤1 integrin (30) are the hallmarks of vascular inflammation and smooth muscle neoplasia. Intriguingly, recent studies also show a robust up-regulation of tTG during vasculo-proliferative conditions in the vessel wall (18).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Platelet-derived Growth Factor Receptor Function by Integrin-associated Cell Surface Transglutaminase

Zemskov¹,

Loukinova²,

Mikhailenko³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

A functional collaboration between growth factor receptors such as platelet derived growth factor receptor (PDGFR) and integrins is required for effective signal transduction in response to soluble growth factors. However, the mechanisms of synergistic PDGFR/integrin signaling remain poorly understood. Our previous work showed that cell surface tissue transglutaminase (tTG) induces clustering of integrins and amplifies integrin signaling by acting as an integrin binding adhesion coreceptor for fibronectin. Here we report that in fibroblasts tTG enhances PDGFR-integrin association by interacting with PDGFR and bridging the two receptors on the cell surface. The interaction between tTG and PDGFR reduces cellular levels of the receptor by accelerating its turnover. Moreover, the association of PDGFR with tTG causes receptor clustering, increases PDGF binding, promotes adhesion-mediated and growth factor-induced PDGFR activation, and up-regulates downstream signaling. Importantly, tTG is required for efficient PDGF-dependent proliferation and migration of fibroblasts. These results reveal a previously unrecognized role for cell surface tTG in the regulation of the joint PDGFR/integrin signaling and PDGFR-dependent cell responses. Adhesion of cells to the extracellular matrix (ECM)2 regulates a wide range of cellular processes, including cell survival, growth, migration, and differentiation. A central paradigm in the field entails both physical association and functional collaboration between integrins and growth factor receptors (GFRs) in the regulation of cell responses to the ECM and soluble growth factors (1). In particular, the engagement of ␤1 and ␣v␤3 integrins with ECM ligands transiently activates plateletderived growth factor (PDGF) receptor-tyrosine kinase even in

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of Platelet-derived Growth Factor Receptor Function by Integrin-associated Cell Surface Transglutaminase

Zemskov¹,

Loukinova²,

Mikhailenko³

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…These cytokines and chemokines are released by alveolar macrophages and have an important role in LIRI, causing an upregulation of adhesion molecules (19), endothelial cell activation (61), decreasing the sensitivity of vascular smooth muscle cells for vasoactive signals (both dilatation and constriction) (110), and trafficking leukocytes to sites of inflammation (130). Macrophages are the initial source of TNF-␣ and the main producers of monocyte chemoattractant protein-1 in the lung (212).…”

Section: H1288 Molecular Mechanisms Of Lung Ischemia-reperfusion Injurymentioning

confidence: 99%

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

Hengst

Gielis

Lin

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

308

279

View full text Add to dashboard Cite

Lung ischemia-reperfusion injury remains one of the major complications after cardiac bypass surgery and lung transplantation. Due to its dual blood supply system and the availability of oxygen from alveolar ventilation, the pathogenetic mechanisms of ischemia-reperfusion injury in the lungs are more complicated than in other organs, where loss of blood flow automatically leads to hypoxia. In this review, an extensive overview is given of the molecular and cellular mechanisms that are involved in the pathogenesis of lung ischemia-reperfusion injury and the possible therapeutic strategies to reduce or prevent it. In addition, the roles of neutrophils, alveolar macrophages, cytokines, and chemokines, as well as the alterations in the cell-death related pathways, are described in detail. pulmonary; lung transplantation; ventilated ischemia IN THE PAST, THE LUNG WAS thought to be relatively resistant to ischemia because of its dual circulation and the availability of oxygen from alveolar ventilation. However, the depletion of lung oxygenation by stopping the ventilation leads to the same degree of lung impairment as a decrease in mechanotransduction by loss of blood flow, as determined by increases in vascular pressure and permeability (11), indicating that any deficiency from oxygenation or mechanotransduction can have significant repercussions (149).Reperfusion of the ischemic lung is a double-edged sword. Reestablishing the perfusion of the ischemic lung is absolutely required to maintain the viability of the lung, but reperfusion itself can trigger a complex cascade of events, the so-called pulmonary ischemia-reperfusion injury (LIRI) (48), characterized by increased microvascular permeability (Pvasc), increased pulmonary vascular resistance (PVR), pulmonary edema, impaired oxygenation, and pulmonary hypertension. Ischemia of the lung, without loss of ventilation, results in a complex pathophysiological situation and, therefore, is not comparable with ischemia in other organs. During ventilated ischemia, for example, the adenosine triphosphate (ATP) levels remain normal while reactive oxygen species (ROS) are formed (70), illustrating aspects of complexity of the pathophysiology of ventilated and anoxic lung ischemia. Therefore, a distinction should be made between ventilated ischemia, meaning a loss of blood flow, and anoxia/reoxygenation, indicating the loss of oxygenation and/or perfusion. In this review, the terms anoxia/reoxygenation and ventilated ischemia will be used, if the specific model is known and/or the mechanism is suggested to be model specific. Ischemia alone will be used, if it applies for both mechanisms, if the specific model is not known, or the research involves other organs.Complete and prolonged lung anoxia for up to several hours is unavoidable during lung transplantation, with dire consequences. Reperfusion of the transplanted lung can lead to nonspecific alveolar damage, pulmonary edema, and hypoxemia within 72 h after lung transplantation. Even with the advancements in lung preservati...

show abstract

“…Integrin α5β1 is highly expressed on vSMCs and has been shown to promote proliferation, migration and switching of vSMCs from a more 'contractile' to a 'synthetic' phenotype (Hedin and Thyberg, 1987;Barillari et al, 2001;Davenpeck et al, 2001;Rensen et al, 2007). Similarly, αv integrins (in particular αvβ3) have been implicated in controlling vSMC migration, de-differentiation, contractility, proliferation and apoptosis (Liaw et al, 1995;D'Angelo et al, 1997;Panda et al, 1997;Dahm and Bowers, 1998).…”

Section: Introductionmentioning

confidence: 99%

α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo

et al. 2015

View full text Add to dashboard Cite

The RGD-binding α5 and αv integrins have been shown to be key regulators of vascular smooth muscle cell (vSMC) function in vitro. However, their role on vSMCs during vascular development in vivo remains unclear. To address this issue, we have generated mice that lack α5, αv or both α5 and αv integrins on their vSMCs, using the SM22α-Cre transgenic mouse line. To our surprise, neither α5 nor αv mutants displayed any obvious vascular defects during embryonic development. By contrast, mice lacking both α5 and αv integrins developed interrupted aortic arches, large brachiocephalic/ carotid artery aneurysms and cardiac septation defects, but developed extensive and apparently normal vasculature in the skin. Cardiovascular defects were also found, along with cleft palates and ectopically located thymi, in Wnt1-Cre α5/αv mutants, suggesting that α5 and αv cooperate on neural crest-derived cells to control the remodelling of the pharyngeal arches and the septation of the heart and outflow tract. Analysis of cultured α5/αv-deficient vSMCs suggests that this is achieved, at least in part, through proper assembly of RGD-containing extracellular matrix proteins and the correct incorporation and activation of latent TGF-β.

show abstract

Inflammatory cytokines stimulate vascular smooth muscle cells locomotion and growth by enhancing α5β1 integrin expression and function

Cited by 64 publications

References 29 publications

Regulation of Platelet-derived Growth Factor Receptor Function by Integrin-associated Cell Surface Transglutaminase

Regulation of Platelet-derived Growth Factor Receptor Function by Integrin-associated Cell Surface Transglutaminase

Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process

α5 and αv integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo

Contact Info

Product

Resources

About