| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2013;5(4):427-440
Original Article
SUMO1 regulates endothelial function by modulating the overall sig-
nals in favor of angiogenesis and homeostatic responses
Ping Yang, Yushan Zhang, Junfa Xu, Shu Zhang, Qilin Yu, Junfeng Pang, Xiaoquan Rao, Michal Kuczma, Mario B
Marrero, David Ful-ton, Piotr Kraj, Yunchao Su, Cong-Yi Wang
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, 1095 Jiefang Ave, Wuhan 430030, China; The Center for Biotechnology and Genomic Medicine,
Georgia Regents University, 1120 15th Street, CA4098, Augusta, GA 30912, USA; Department of Clinical
Immunology, Institute of Laboratory Medicine, Guangdong Medical College, 1 Xincheng Road, Dongguan,
523808, China; Vascular Biology Center, Georgia Regents University, Augusta, GA, USA; Department of
Pharmacology and Toxicology, Georgia Regents University, Augusta, GA, USA. The first two authors contributed
equally to this work.
Received April 4, 2013; Accepted April 25, 2013; Epub May 24, 2013; Published June 1, 2013
Abstract: As a versatile regulatory mechanism, sumoylation has been found to be essential for ordered diverse
cellular processes. However, the exact impact of sumoylation on endothelial function largely remained elusive.
Here we investigated the role of small ubiquitin-like modifier 1 (SUMO1) mediated sumoylation in the regulation
of endothelial function by examining its effect on angiogenesis and homeostatic responses. Adenoviral-mediated
SUMO1 expression in porcine aortic endothelial cells (PAECs) dose-dependently promoted proliferation,
migration and tube formation. In line with these results in PAECs, Matrigel plug assays in SUMO1 transgenic
mice demonstrated a significant higher capacity for vascular neogenesis as compared with that of control
littermates. Moreover, SUMO1 expression protected PAECs from serum starvation or H2O2-induced apoptosis.
Mechanistic studies demonstrated that SUMO1 sumoylation modulates ERK1/2 activation and MMP13
expression as well as Jak2/STAT5 signaling to promote angiogenesis. SUMO1 sumoylation also suppressed
NFκB and c-JUN transcriptional activity to provide protection for PAECs against oxidative stress-induced
apoptosis. Given that sumoylation is a reversible process, dynamic regulation of the sumoylation function could
be a novel strategy to modulate endothelial function in disease states. (AJTR1304003).
Keywords: Sumoylation, endothelial cells, angiogenesis, SUMO1
Address correspondence to: Dr. Cong-Yi Wang, the Center for Biomedical Research, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, China. E-
mail: cwang@gru.edu
Original Article
SUMO1 regulates endothelial function by modulating the overall sig-
nals in favor of angiogenesis and homeostatic responses
Ping Yang, Yushan Zhang, Junfa Xu, Shu Zhang, Qilin Yu, Junfeng Pang, Xiaoquan Rao, Michal Kuczma, Mario B
Marrero, David Ful-ton, Piotr Kraj, Yunchao Su, Cong-Yi Wang
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science
and Technology, 1095 Jiefang Ave, Wuhan 430030, China; The Center for Biotechnology and Genomic Medicine,
Georgia Regents University, 1120 15th Street, CA4098, Augusta, GA 30912, USA; Department of Clinical
Immunology, Institute of Laboratory Medicine, Guangdong Medical College, 1 Xincheng Road, Dongguan,
523808, China; Vascular Biology Center, Georgia Regents University, Augusta, GA, USA; Department of
Pharmacology and Toxicology, Georgia Regents University, Augusta, GA, USA. The first two authors contributed
equally to this work.
Received April 4, 2013; Accepted April 25, 2013; Epub May 24, 2013; Published June 1, 2013
Abstract: As a versatile regulatory mechanism, sumoylation has been found to be essential for ordered diverse
cellular processes. However, the exact impact of sumoylation on endothelial function largely remained elusive.
Here we investigated the role of small ubiquitin-like modifier 1 (SUMO1) mediated sumoylation in the regulation
of endothelial function by examining its effect on angiogenesis and homeostatic responses. Adenoviral-mediated
SUMO1 expression in porcine aortic endothelial cells (PAECs) dose-dependently promoted proliferation,
migration and tube formation. In line with these results in PAECs, Matrigel plug assays in SUMO1 transgenic
mice demonstrated a significant higher capacity for vascular neogenesis as compared with that of control
littermates. Moreover, SUMO1 expression protected PAECs from serum starvation or H2O2-induced apoptosis.
Mechanistic studies demonstrated that SUMO1 sumoylation modulates ERK1/2 activation and MMP13
expression as well as Jak2/STAT5 signaling to promote angiogenesis. SUMO1 sumoylation also suppressed
NFκB and c-JUN transcriptional activity to provide protection for PAECs against oxidative stress-induced
apoptosis. Given that sumoylation is a reversible process, dynamic regulation of the sumoylation function could
be a novel strategy to modulate endothelial function in disease states. (AJTR1304003).
Keywords: Sumoylation, endothelial cells, angiogenesis, SUMO1
Address correspondence to: Dr. Cong-Yi Wang, the Center for Biomedical Research, Tongji Hospital, Tongji
Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, China. E-
mail: cwang@gru.edu
 | |  | |  | |  | |  | |  | |  |