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Actin cytoskeletal rearrangement and dysfunction due to activation of the receptor for advanced glycation end products is inhibited by thymosin beta 4
Author(s) -
Kim Sokho,
Kwon Jungkee
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.287045
Subject(s) - microbiology and biotechnology , actin cytoskeleton , cytoskeleton , actin remodeling , rage (emotion) , actin , profilin , glycation , biology , chemistry , receptor , cell , biochemistry , neuroscience
Key points Thymosin beta 4 (Tβ 4 ) attenuates the vascular cellular toxicity induced by advanced glycation end products (AGEs) in human umbilical vein endothelial cells (HUVECs). Tβ 4 reduces expression of both the receptor of AGEs (RAGE) and the filamentous actin (F‐actin) to globular actin (G‐actin) ratio. RAGE expression was regulated by actin cytoskeleton involved in Tβ 4 . Tβ 4 attenuates the vascular cellular toxicity induced by AGEs via remodelling of the actin cytoskeleton. AGEs attenuate vascular‐like tube formation of HUVECs, which is reversed by Tβ 4 via remodelling of the actin cytoskeleton.Abstract The receptor of advanced glycation end products (RAGE) is a cell‐surface receptor that is a key factor in the pathogenesis of diabetic complications, including vascular disorders. Dysfunction of the actin cytoskeleton contributes to disruption of cell membrane repair in response to various type of endothelial cell damage. However, mechanism underlying RAGE remodelling of the actin cytoskeleton, by which globular actin (G‐actin) forms to filamentous actin (F‐actin), remains unclear. In this study we examined the role of thymosin beta 4 (Tβ 4 ) – which binds to actin, blocks actin polymerization, and maintains the dynamic equilibrium between G‐actin and F‐actin in human umbilical vein endothelial cells (HUVECs) – in the response to RAGE. Tβ 4 increased cell viability and decreased levels of reactive oxygen species in HUVECs incubated with AGEs. Tβ 4 reduced the expression of RAGE, consistent with a down‐regulation of the F‐actin to G‐actin ratio. The effect of remodelling of the actin cytoskeleton on RAGE expression was clarified by adding Phalloidin, which stabilizes F‐actin. Moreover, small interfering RNA was used to determine whether intrinsic Tβ 4 regulates RAGE expression in the actin cytoskeleton. The absence of intrinsic Tβ 4 in HUVECs evoked actin cytoskeleton disorder and increased RAGE expression. These findings suggest that regulation of the actin cytoskeleton by Tβ 4 plays a pivotal role in the RAGE response to AGEs.