Tumour Necrosis Factor Α Alters the Expression of Connexin43, Connexin40, and Connexin37, in Human Umbilical Vein Endothelial Cells

Rijen, Harold V. M. van; Kempen, Marjan J. A. van; Postma, Sjoerd; Jongsma, Habo J.

doi:10.1006/cyto.1997.0287

Cited by 127 publications

(94 citation statements)

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“…Gap junctional coupling between human monocytes and endothelial cells seems crucial for monocyte/macrophage transmigration in a blood-brain barrier model [51]. Moreover, the expression of three connexin isoforms, namely Cx37, Cx40 and Cx43, has been reported in circulating blood cells as well as in vascular endothelial cells [52,53]. The expression of connexins in blood and endothelial cells is modulated by pro-inflammatory agents such as LPS and TNF-α  [51] and the switch from Cx37/Cx40 to Cx43 expression takes place in endothelial cells during inflammation [54].…”

Section: Discussionmentioning

confidence: 99%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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Tumour development is a process resulting from the disturbance of various cellular functions including cell proliferation, adhesion and motility. While the role of these cell parameters in tumour promotion and progression has been widely recognized, the mechanisms that influence gap junctional coupling during tumorigenesis remain elusive. Neoplastic cells usually display decreased levels of connexin expression and/or gap junctional coupling. Thus, impaired intercellular communication via gap junctions may facilitate the release of a potentially neoplastic cell from the controlling regime of the surrounding tissue, leading to tumour promotion. However, recent data indicates that metastatic tumour cell lines are often characterized by relatively high levels of connexin expression and gap junctional coupling. This review outlines current knowledge on the role of connexins in tumorigenesis and the possible mechanisms of the interference of gap junctional coupling with the processes of tumour invasion and metastasis. GAP JUNCTIONS -THEIR STRUCTURE AND BASIC FUNCTIONS IN TISSUE HOMEOSTASISGap junctions are aqueous intercellular channels which directly link the cytoplasmic compartments of adjacent cells (Fig. 1). These channels are formed upon the docking of two connexons, hexameric hemichannels built of proteins belonging to the connexin family [1]. Gap junctions are present in almost all vertebrate tissues, where they permit the intercellular exchange of small (< 1 kDa) metabolites and second messengers, and thus synchronise cellular functions in tissues [2][3][4]. Representative examples of the synchronising function of gap junctional coupling in tissues include electrical and metabolic coupling. In the former, gap junctions take part in the intercellular spreading of membrane depolarisation by permitting the rapid cell-to-cell transfer of calcium ions between cardiac muscle cells [1], or by constituting electrical synapses in the nervous system [5]. Metabolic coupling is established when the stimulation of one cell is propagated to a cluster of cells through the spreading of active substances, such as monosaccharides and cyclic nucleotides [2,6]. While electrical coupling predominantly synchronizes cell functions in excitable tissues, metabolic coupling affects the homeostasis of a spectrum of multicellular systems, including both excitable and non-excitable tissues. The crucial role of gap junctions in the regulation of tissue homeostasis is illustrated by the functional impairment of many vertebrate tissues occurring when there is deficient gap junctional communication [7,8]. For instance, disruption of the function of the gene encoding Cx32 is associated with the progressive degeneration of the peripheral nerves, resulting from the impairment of the diffusion of nutrients and signalling molecules between the perinuclear and periaxonal Schwann cell cytoplasm [for review see [9]. Furthermore, abnormalities have been observed in Cx32-deficient mouse livers: Cx32 disruption leads to a decrease in the disc...

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Section: Discussionmentioning

confidence: 99%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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“…Inflammatory mediators, such as tumor necrosis factor- 12,26 and lipopolysaccharide, 27 induce leukocyte adhesion molecules such as VCAM-1, but also downregulate connexin37 expression in vascular ECs. 28,29 The inhibition of connexin37 expression by CB thus seems to be associated with EC inflammatory process such as adhesion and/or transmigration of leukocytes. Finally, a genetic polymorphism has been identified in the human connexin37 protein, apparently representing a prognostic marker for atherosclerotic plaque development.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying Nano-Sized Air-Pollution-Mediated Progression of Atherosclerosis Carbon Black Causes Cytotoxic Injury/Inflammation and Inhibits Cell Growth in Vascular Endothelial Cells

Yamawaki¹,

Iwai²

2006

Circ J

128

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“…For example, increased mechanical load enhances Cx43 expression, 23 and treatment with tumor necrosis factor-␣, a cytokine promoting endothelial cell migration, leads to upregulation of Cx43 and downregulation of Cx37 and Cx40 in human umbilical vein endothelial cells. 25 In addition, Cx43 and Cx37 in cultured bovine aortic endothelial cells are reported to be differentially regulated by cell density and growth status 21 ; although levels of Cx43 mRNA and protein were high in subconfluent cells and low in confluent cells, the opposite applied to Cx37 mRNA, which was present only in low amounts until the cultures became confluent. In contrast, in the present study, Cx37 and Cx43 spots increased progressively during the course of endothelial regeneration in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…6,18 -21 The specific pattern of connexin expression may also be differentially affected by physical and chemical factors, such as mechanical load, blood sugar level, growth factors, and cytokines. [21][22][23][24][25] However, current knowledge about the role of each connexin in the endothelial cell is limited, and most studies have been limited to examination of 1 or 2 connexins. Previous studies of regenerating vascular endothelium in animal models have been confined to morphometric measurement of the size and number of gap junctions, and corresponding in vitro studies have been confined to Cx43.…”

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Multiple Connexin Expression in Regenerating Arterial Endothelial Gap Junctions

Yeh

Lai²,

Chang³

et al. 2000

ATVB

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Abstract-Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery (PϽ0.05). Double-label analysis showed that even though colocalization of connexins to the same gap-junctional spot is a common feature, the extent of colocalization was time dependent (Ͼ80% in the intact artery at postinjury day 28 and Ͻ70% at postinjury days 7 and 14, PϽ0.01). We conclude that distinct alterations in expression of the 3 connexins are associated with regeneration of the arterial endothelium in situ, implying different intercellular communication requirements during the various phases of the healing process.

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Tumour Necrosis Factor Α Alters the Expression of Connexin43, Connexin40, and Connexin37, in Human Umbilical Vein Endothelial Cells

Cited by 127 publications

References 0 publications

The stage-specific function of gap junctions during tumourigenesis

The stage-specific function of gap junctions during tumourigenesis

Mechanisms Underlying Nano-Sized Air-Pollution-Mediated Progression of Atherosclerosis Carbon Black Causes Cytotoxic Injury/Inflammation and Inhibits Cell Growth in Vascular Endothelial Cells

Multiple Connexin Expression in Regenerating Arterial Endothelial Gap Junctions

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