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Permanent link (DOI): https://doi.org/10.7939/R3B27Q03F

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Investigating the role of coiled-coil domain containing protein 3 (CCDC3), a novel secreted protein, in endothelial inflammation Open Access

Descriptions

Other title
Subject/Keyword
HMEC
HUVEC
Inflammation
VCAM-
NF-kB
TNF
Atherosclerosis
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Azad, Abul K
Supervisor and department
Baksh, Shairaz (Pedritics)
Davidge, Sandra T (Ob/Gyn, Physiology)
Fu, Yangxin (Supervisor)
Examining committee member and department
Underhill, Alan (Oncology)
Chan, Gordon (Oncology)
Godbout, Roseline (Oncology)
Department
Department of Oncology
Specialization
Cancer Sciences
Date accepted
2015-05-20T13:24:24Z
Graduation date
2015-11
Degree
Master of Science
Degree level
Master's
Abstract
Endothelial inflammation is critical in the initiation and progression of atherosclerosis and other cardiovascular diseases (CVDs). Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine that induces endothelial inflammation via activation of nuclear factor κB (NF-κB) signaling. Coiled-coil domain containing 3 (CCDC3) is a newly identified secretory protein mainly expressed in endothelial cells (ECs) and in adipose tissues. However, the function of CCDC3 in ECs is unclear. A published paper showed that TNF-α downregulates CCDC3 expression in ECs. We therefore investigated the role of CCDC3 in TNF-α-induced inflammatory response in ECs. In response to inflammation, ECs express adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) that recruit leukocytes to the sites of infection or injury. In our study we found that stable overexpression of CCDC3 decreased, while stable knockdown of CCDC3 increased TNF-α-induced expression of VCAM-1 at the mRNA and protein levels in ECs. Mechanistically, stable overexpression of CCDC3 decreased TNF-α-induced p65 and p50 nuclear translocation and nuclear NF-κB activity, suggesting that CCDC3 attenuates TNF-α-induced gene expression by inhibiting NF-κB signaling in ECs. Importantly, we found that CCDC3 in the conditioned medium (CM) as well as the purified CCDC3 decreased TNF-α-induced expression of VCAM-1 in receiving ECs, suggesting that CCDC3 has a paracrine/autocrine function. Interestingly, CCDC3 in CM can enter the receiving ECs. Taken together, our work demonstrates that CCDC3 represses TNF-α/NF-κB-induced pro-inflammatory response in ECs, suggesting a potential anti-inflammatory and atheroprotective role of CCDC3 in vascular ECs.
Language
English
DOI
doi:10.7939/R3B27Q03F
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Azad, A.K., et al., Coiled-coil domain containing 3 (CCDC3) represses tumor necrosis factor-alpha/nuclear factor kappaB-induced endothelial inflammation. Cell Signal, 2014. 26(12): p. 2793-800.

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