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Control of adipogenic transformation in vascular smooth muscle cells by the transglutaminase 2/b‐catenin signaling axis
Author(s) -
Beazley Kelly E,
Williams Katelyn,
Nurminskaya Maria V
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.530.4
Subject(s) - adipogenesis , microbiology and biotechnology , phenotype , signal transduction , catenin , tissue transglutaminase , lipid droplet , adipocyte , chemistry , beta catenin , biology , medicine , endocrinology , wnt signaling pathway , biochemistry , enzyme , adipose tissue , mesenchymal stem cell , gene
In atherosclerosis, smooth muscle cells (SMCs) undergo a unique process known as “phenotype modulation,” transitioning from a quiescent, contractile phenotype to an adipocyte‐like state. Increased b‐catenin signaling has been observed in atherosclerotic plaques, and deficiency of transglutaminase 2 (TG2) – an endogenous activator of b‐catenin – reduces lipid accumulation in the mouse model of atherosclerosis. Here we examined whether inhibition of the TG2/b‐catenin signaling axis in SMCs can prevent their phenotypic transition. Adipogenesis was induced in aortic SMCs using a high‐lipid culture medium, and detected histologically by Oil Red‐O and on the molecular level by expression of adipogenic markers. Pronounced adipogenic differentiation was detected in 6 day‐cultures. Activation of both TG2 enzyme and b‐catenin signaling occurs 4 days earlier, suggesting that this signaling axis may mediate the transition. Inhibition of TG2 by genetic ablation or pharmacologically suppressed both lipid accumulation and b‐catenin activation in aortic SMCs. In addition, direct inhibition of b‐catenin signaling with siRNA for b‐catenin efficiently prevented SMC adipogenesis. Together our results support a key role for the TG2/b‐catenin signaling axis in the transition of SMCs to an adipogenic phenotype. This research was supported by NIH grants R01HL093305 and T32AR007592.