Cell-permeable mitochondrial ubiquinol-cytochrome c reductase binding protein induces angiogenesis in vitro and in vivo

Junghwa Chang, Hye Jin Jung, Hyun Ji Park, Seung Woo Cho, Sang Kyou Lee, Ho Jeong Kwon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ubiquinol-cytochrome c reductase binding protein (UQCRB), a component of the mitochondrial complex III, has been recently implicated in angiogenesis. Targeting mitochondria to balance vascular homeostasis has been widely recognized. However, the effect of UQCRB replenishment by direct delivery remains unknown. To explore the biological function of UQCRB in angiogenesis, a novel protein transduction domain (PTD)-conjugated UQCRB fusion protein was generated. PTD-UQCRB localized to mitochondria as does endogenous UQCRB. Treatment with PTD-UQCRB generated mitochondrial reactive oxygen species (mROS) without cytotoxicity, following hypoxia inducible factor-1α (HIF-1α) stabilization and downstream vascular endothelial growth factor (VEGF) expression. Accordingly, PTD-UQCRB induced angiogenesis in vitro and PTD-UQCRB pro-angiogenic activity was further validated in matrigel plug assay and in cutaneous wound-healing mouse models in vivo. Together, these results demonstrate that UQCRB plays a role in angiogenesis and the developed cell-permeable PTD-UQCRB can be utilized as a pro-angiogenic agent.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalCancer Letters
Volume366
Issue number1
DOIs
Publication statusPublished - 2015 Sep 28

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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