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Title: The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing

Abstract

Research highlights: {yields} Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90{alpha} secretion from endothelial cells. {yields} Secreted Hsp90{alpha} localizes on the leading edge of activated endothelial cells. {yields} Secreted Hsp90{alpha} promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90{alpha} (Hsp90{alpha}) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90{alpha} can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90{alpha} from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90{alpha} in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90{alpha} but not Hsp90{beta} is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90{alpha} localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90{alpha} neutralizing antibodies reverse the effect. Furthermore, usingmore » a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90{alpha} localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90{alpha} can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90{alpha} as a stimulator for wound repair.« less

Authors:
 [1];  [1]
  1. National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China)
Publication Date:
OSTI Identifier:
22202695
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 398; Journal Issue: 1; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; ANIMAL TISSUES; ANTIBODIES; CAPILLARIES; GROWTH FACTORS; HEALING; HEAT-SHOCK PROTEINS; HOMEOSTASIS; IN VITRO; IN VIVO; INFECTIOUS DISEASES; MICE; NEOPLASMS; SECRETION; SKIN; WOUNDS

Citation Formats

Song, Xiaomin, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, Luo, Yongzhang, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084. The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.06.046.
Song, Xiaomin, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, Luo, Yongzhang, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, & Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084. The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing. United States. doi:10.1016/J.BBRC.2010.06.046.
Song, Xiaomin, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, Luo, Yongzhang, Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084, and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084. Fri . "The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing". United States. doi:10.1016/J.BBRC.2010.06.046.
@article{osti_22202695,
title = {The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing},
author = {Song, Xiaomin and Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 and Luo, Yongzhang and Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 and Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084},
abstractNote = {Research highlights: {yields} Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90{alpha} secretion from endothelial cells. {yields} Secreted Hsp90{alpha} localizes on the leading edge of activated endothelial cells. {yields} Secreted Hsp90{alpha} promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90{alpha} (Hsp90{alpha}) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90{alpha} can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90{alpha} from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90{alpha} in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90{alpha} but not Hsp90{beta} is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90{alpha} localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90{alpha} neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90{alpha} localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90{alpha} can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90{alpha} as a stimulator for wound repair.},
doi = {10.1016/J.BBRC.2010.06.046},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 398,
place = {United States},
year = {2010},
month = {7}
}