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Nuclear factor {kap...
Nuclear factor {kappa}B-mediated transactivation of telomerase prevents intimal smooth muscle cell from replicative senescence during vascular repair
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Bu, D. X. (författare)
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- Johansson, Maria E, 1977 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Ren, J. (författare)
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visa fler...
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Xu, D. W. (författare)
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Johnson, F. B. (författare)
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Edfeldt, K. (författare)
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Yan, Z. Q. (författare)
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visa färre...
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(creator_code:org_t)
- 2010
- 2010
- Engelska.
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636 .- 1079-5642. ; 30:12, s. 2604-10
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- OBJECTIVE: To gain insights into mechanisms by which intimal hyperplasia interferes with the repair process by investigating expression and function of the catalytic telomerase reverse transcriptase (TERT) subunit after vascular injury. METHODS AND RESULTS: Functional telomerase is essential to the replicative longevity of vascular cells. We found that TERT was de novo activated in the intima of injured arteries, involving activation of the nuclear factor kappaB pathway. Stimulation of the isolated intimal smooth muscle cell (SMC) by basic fibroblast growth factor or tumor necrosis factor alpha resulted in increased TERT activity. This depends on the activation of c-Myc signaling because mutation of the E-box in the promoter or overexpression of mitotic arrest deficient 1 (MAD1), a c-Myc competitor, abrogated the transcriptional activity. Inhibition of nuclear factor kappaB in both intimal SMCs and the injured artery attenuated TERT transcriptional activity through reduction of c-Myc expression. Pharmacological blockade of TERT led to SMC senescence. Finally, depletion of telomerase function in mice resulted in severe intimal SMC senescence after vascular injury. CONCLUSIONS: These results support a model in which vascular injury induces de novo expression of TERT in intimal SMCs via activation of nuclear factor kappaB and upregulation of c-Myc. The resumed TERT activity is critical for intimal hyperplasia.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Aminobenzoic Acids/pharmacology
- Animals
- Binding Sites
- Carotid Artery Injuries/*enzymology/genetics/pathology
- *Cell Aging/drug effects
- *Cell Proliferation/drug effects
- Cells
- Cultured
- Disease Models
- Animal
- Enzyme Inhibitors/pharmacology
- Fibroblast Growth Factor 2/metabolism
- Gene Expression Regulation
- Enzymologic
- Hyperplasia
- I-kappa B Kinase/genetics/metabolism
- Male
- Mice
- Mice
- Knockout
- Myocytes
- Smooth Muscle/drug effects/*enzymology/pathology
- NF-kappa B/*metabolism
- Naphthalenes/pharmacology
- Promoter Regions
- Genetic
- Proto-Oncogene Proteins c-myc/metabolism
- RNA/genetics
- RNA
- Messenger/metabolism
- Rats
- Rats
- Sprague-Dawley
- Telomerase/antagonists & inhibitors/deficiency/genetics/*metabolism
- *Transcriptional Activation
- Transduction
- Genetic
- Tumor Necrosis Factor-alpha/metabolism
- Tunica Intima/drug effects/*enzymology/pathology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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