Nucleotide-binding oligomerization domain protein 2 attenuates ER stress-induced cell death in vascular smooth muscle cells

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Title
Nucleotide-binding oligomerization domain protein 2 attenuates ER stress-induced cell death in vascular smooth muscle cells
Author(s)
M Y Kwon; N Hwang; Seon-Jin Lee; S W Chung
Bibliographic Citation
BMB Reports, vol. 52, no. 11, pp. 665-670
Publication Year
2019
Abstract
Nucleotide-binding oligomerization domain protein 2 (NOD2), an intracellular pattern recognition receptor, plays important roles in inflammation and cell death. Previously, we have shown that NOD2 is expressed in vascular smooth muscle cells (VSMCs) and that NOD2 deficiency promotes VSMC proliferation, migration, and neointimal formation after vascular injury. However, its role in endoplasmic reticulum (ER) stress-induced cell death in VSMCs remains unclear. Thus, the objective of this study was to evaluate ER stress-induced viability of mouse primary VSMCs. NOD2 deficiency increased ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) in VSMCs in the presence of tunicamycin (TM), an ER stress inducer. In contrast, ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) were decreased in NOD2-overexpressed VSMCs. We found that the IRE-1α-XBP1 pathway, one of unfolded protein response branches, was decreased in NOD2-deficient VSMCs and reversed in NOD2-overexpressed VSMCs in the presence of TM. Furthermore, NOD2 deficiency reduced the expression of XBP1 target genes such as GRP78, PDI-1, and Herpud1, thus improving cell survival. Taken together, these data suggest that the induction of ER stress through NOD2 expression can protect against TM-induced cell death in VSMCs. These results may contribute to a new paradigm in vascular homeostasis.
Keyword
Cell deathEndoplasmic reticulum stressNOD2TunicamycinVascular smooth muscle cells
ISSN
1225-8687
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.5483/BMBRep.2019.52.11.176
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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