Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells

Mun, Gyeong In; Boo, Yong Chool

doi:10.1152/ajpheart.00835.2009

Cited by 49 publications

(37 citation statements)

References 33 publications

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“…In the case of senescence in defined body compartments 92,162 , delivering drugs directly to the sites of pathology could avoid side effects. Antibodies raised against senescence-specific surface antigens, such as CD44 in the senescent endothelium 163 , could also be used to direct cytotoxic T cells for killing or to deliver cytotoxic nanoparticles. An intriguing possibility based on recent success in killing cancer cells is that senescent cell antigens could be used to raise T cells in vitro armed with artificial, chimeric antigen receptors (CARs) raised against senescent cell–specific surface antigens for infusion 164 .…”

Section: Therapy-induced Senescencementioning

confidence: 99%

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs

Durik

Baker

et al. 2015

Nat Med

1,684

1,489

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Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

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Section: Therapy-induced Senescencementioning

confidence: 99%

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs

Durik

Baker

et al. 2015

Nat Med

1,684

1,489

View full text Add to dashboard Cite

show abstract

“…With regard to specificity, CD44, the major marker of breast carcinomas CSC-TPC, has been ascribed very divergent roles in different cell types. It is identified as a senescence-induced cell adhesion gene responsible for monocyte recruitment (Mun and Boo, 2010). In lymphoma and lymphoma cell lines, it is an epigenetically suppressed inducer of apoptosis (Eberth et al, 2010).…”

Section: Csc-tpc Biomarkersmentioning

confidence: 99%

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Floor¹,

Staveren²,

et al. 2011

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“…When endothelial cells are activated by an inflammatory stimulus, they express intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), 2 E-selectin, and other selective adhesion molecules that mediate the heterotypic binding between leukocytes and endothelial cells, the primary event of atherosclerotic lesion formation (2). Endothelial cell senescence also increases monocyte recruitment, independently of acute inflammatory stimuli, by increasing the expression of adhesion molecules such as CD44 (3). Therefore, the "health" of endothelial cells is essential for the prevention of the initial events of atherosclerosis.…”

mentioning

confidence: 99%

Endothelial Argininosuccinate Synthetase 1 Regulates Nitric Oxide Production and Monocyte Adhesion under Static and Laminar Shear Stress Conditions

Mun

Kim

Lee

et al. 2011

Journal of Biological Chemistry

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Laminar shear stress (LSS) is known to increase endothelial nitric oxide (NO) production, which is essential for vascular health, through expression and activation of nitric oxide synthase 3 (NOS3). Recent studies demonstrated that LSS also increases the expression of argininosuccinate synthetase 1 (ASS1) that regulates the provision of L-arginine, the substrate of NOS3. It was thus hypothesized that ASS1 might contribute to vascular health by enhancing NO production in response to LSS. This hypothesis was pursued in the present study by modulating NOS3 and ASS1 levels in cultured endothelial cells. Exogenous expression of either NOS3 or ASS1 in human umbilical vein endothelial cells increased NO production and decreased monocyte adhesion stimulated by tumor necrosis factor-␣ (TNF-␣). The latter effect of overexpressed ASS1 was reduced when human umbilical vein endothelial cells were co-treated with small interfering RNAs (siRNAs) for ASS1 or NOS3. SiRNAs of NOS3 and ASS1 attenuated the increase of NO production in human aortic endothelial cells stimulated by LSS (12 dynes⅐cm ؊2 ) for 24 h. LSS inhibited monocyte adhesion to human aortic endothelial cells stimulated by TNF-␣, but this effect of LSS was abrogated by siRNAs of NOS3 and ASS1 that recovered the expression of vascular cell adhesion molecule-1. The current study suggests that the expression of ASS1 harmonized with that of NOS3 may be important for the optimized endothelial NO production and the prevention of the inflammatory monocyte adhesion to endothelial cells.Atherosclerosis is a chronic disease characterized by the accumulation of lipids and fibrous elements in the intimal lining of the large-and medium-sized arteries. Its development takes place step-by-step involving endothelial cell injury, migration of inflammatory cells, deposition of lipids and proliferation of smooth muscle cells, growth of this mass (atheroma) into the vessel lumen, and rupture of the plaque with subsequent thrombosis (1). When endothelial cells are activated by an inflammatory stimulus, they express intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), 2 E-selectin, and other selective adhesion molecules that mediate the heterotypic binding between leukocytes and endothelial cells, the primary event of atherosclerotic lesion formation (2). Endothelial cell senescence also increases monocyte recruitment, independently of acute inflammatory stimuli, by increasing the expression of adhesion molecules such as CD44 (3). Therefore, the "health" of endothelial cells is essential for the prevention of the initial events of atherosclerosis.Laminar shear stress (LSS) due to pulsatile blood flow is known to provide beneficial effects on vascular health (4 -6). Indeed, the straight regions of the arteries that experience pulsatile LSS are usually protected from the formation of atherosclerotic lesions (7,8). The anti-atherogenic effects of pulsatile LSS and steady LSS (the latter does not occur in arteries in vivo but is being studied in vitro) have...

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Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells

Abstract: Mun GI, Boo YC. Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells.

Cited by 49 publications

References 33 publications

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Endothelial Argininosuccinate Synthetase 1 Regulates Nitric Oxide Production and Monocyte Adhesion under Static and Laminar Shear Stress Conditions

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