title: Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction.
abstract: Endothelial cell function is critical for angiogenic balance in both physiological and pathological conditions, such as wound healing and cancer, respectively. We report here that soluble heat shock protein beta-1 (HSPB1) is released primarily from endothelial cells (ECs), and plays a key role in regulating angiogenic balance via direct interaction with vascular endothelial growth factor (VEGF). VEGF-mediated phosphorylation of intracellular HSPB1 inhibited the secretion of HSPB1 and their binding activity in ECs. Interestingly, co-culture of tumor ECs with tumor cells decreased HSPB1 secretion from tumor ECs, suggesting that inhibition of HSPB1 secretion allows VEGF to promote angiogenesis. Additionally, neutralization of HSPB1 in a primary mouse sarcoma model promoted tumor growth, indicating the anti-angiogenic role of soluble HSPB1. Overexpression of HSPB1 by HSPB1 adenovirus was sufficient to suppress lung metastases of CT26 colon carcinoma in vivo, while neutralization of HSPB1 promoted in vivo wound healing. While VEGF-induced regulation of angiogenesis has been studied extensively, these findings illustrate the key contribution of HSPB1-VEGF interactions in the balance between physiological and pathological angiogenesis.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hae-Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Choi
authors.forename: Yeung Bae
authors.initials: YB
authors.lastname: Jin
authors.forename: Ho Jung
authors.initials: HJ
authors.lastname: An
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
authors.forename: Sam S
authors.initials: SS
authors.lastname: Yoon
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse