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The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis.


ABSTRACT: Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation. Mechanistically, inflammation-induced SENP1 promotes the deSUMOylation of GATA2 and I?B? in endothelial cells, resulting in increased GATA2 stability, promoter-binding capability and NF-?B activity, which leads to augmented endothelial activation and inflammation. Therefore, upon inflammation, endothelial SENP1-mediated SUMOylation drives GA by regulating the synergistic effect of GATA2 and NF-?B and consequent endothelial dysfunction.

SUBMITTER: Qiu C 

PROVIDER: S-EPMC5461500 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis.

Qiu Cong C   Wang Yuewen Y   Zhao Haige H   Qin Lingfeng L   Shi Yanna Y   Zhu Xiaolong X   Song Lin L   Zhou Xiaofei X   Chen Jian J   Zhou Hong H   Zhang Haifeng H   Tellides George G   Min Wang W   Yu Luyang L  

Nature communications 20170601


Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta tran  ...[more]

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