Soluble HSPB1 regulates VEGF-mediated angiogenesis through their direct interaction

Yoon Jin Lee, Hae Jun Lee, Seo Hyun Choi, Yeung Bae Jin, Ho Jung An, Jin Hyoung Kang, Sam S. Yoon, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 VEGFinduced 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.

Original languageEnglish
Pages (from-to)229-242
Number of pages14
JournalAngiogenesis
Volume15
Issue number2
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
Acknowledgments We thank Dr. Sandra Ryeom (University of Pennsylvania Medical School) for helpful discussions and Dr. Christiana DelloRusso for assistance editing the manuscript. This work was supported by the Nuclear Research and Development Program (Grant No. M2AMA006), Basic Science Research Program (Grant No. R1A4A002), and Mid-career Researcher Program (Grat No. 2011-0013364) of the National Research Foundation of Korea (NRF) funded by the Korean Ministry of Education, Science, and Technology (MEST).

Keywords

  • Angiogenic balance
  • Endothelial cell (EC)
  • Heat shock protein 25/27 (HSPB1)
  • Vascular endothelial growth (VEGF)

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