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HMGB1 contributes to the irradiation‐induced endothelial barrier injury through receptor for advanced glycation endproducts (RAGE)
Author(s) -
Zhou Haihong,
Jin Congli,
Cui Lili,
Xing Huaijie,
Liu Jun,
Liao Wang,
Liao Haojie,
Yu Yangsheng
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26341
Subject(s) - hmgb1 , chemistry , rage (emotion) , mapk/erk pathway , glycation , receptor , endothelium , barrier function , tight junction , microbiology and biotechnology , signal transduction , endothelial stem cell , cancer research , biology , biochemistry , endocrinology , in vitro , neuroscience
This study aimed to investigate whether HMGB1 (high mobility group box‐1 protein) and receptor for advanced glycation end products (RAGE) were involved in the irradiation‐induced endothelial barrier damage and their mechanism. We constructed the damage model of endothelium barrier model with bEnd.3 cells. The permeability of endothelial barrier was detected by sodium fluorescein (Na‐F) permeation test, and the irradiation dose which could induce permeability transition was determined by being exposed to different irradiation doses (5, 10, 15, 20 Gy). MTT assay was applied to detect cell viability under different concentrations of HMGB1 , glycyrrhizic acid (GA, a specific inhibitor of HMGB1 ), and FPS‐ZM1 (a blood‐brain‐barrier permeant blocker of RAGE V domain‐mediated ligand binding). The expression of HMGB1 , RAGE, and related molecules involved in MAPK signaling pathway, MMP‐2, MMP‐9, ZO‐1, and claudin 5 of differently treated groups were measured by qRT‐PCR, western blot, and immunofluorescence. Cells possessed stable endothelial barrier function on 4–7 days after seeded on transwell plates. The permeability of endothelial barrier would change under at least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the permeability. After irradiation, the expressions of HMGB1 and RAGE increased and MAPK signal pathway was activated. Meanwhile, MMP‐2 and MMP‐9 were overexpressed, while the expression of tight junction proteins ZO‐1 and claudin 5 was decreased. Radiation could activate MAPK signaling pathway through promoting the expression of HMGB1 and RAGE, which further led to endothelial barrier injury and changed its permeability.