Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport

K. Ozawa, T. Kondo, O. Hori, Y. Kitao, David Stern, W. Eisenmenger, S. Ogawa, T. Ohshima

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Abstract

Expression of angiogenic factors such as VEGF under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis. Local administration of ORP150 sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased VEGF antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of ORP150 expression caused retention of VEGF antigen within the endoplasmic reticulum (ER), while overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants. Taken together, these data suggest an important role for ORP150 in the setting of impaired wound repair and identify a key, inducible chaperone-like molecule in the ER. This novel facet of the angiogenic response may be amenable to therapeutic manipulation.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalJournal of Clinical Investigation
Volume108
Issue number1
DOIs
StatePublished - Jul 24 2001

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Wound Healing
Vascular Endothelial Growth Factor A
Endoplasmic Reticulum
Wounds and Injuries
Macrophages
Antigens
Angiogenesis Inducing Agents
Adenoviridae
oxygen-regulated proteins
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport. / Ozawa, K.; Kondo, T.; Hori, O.; Kitao, Y.; Stern, David; Eisenmenger, W.; Ogawa, S.; Ohshima, T.

In: Journal of Clinical Investigation, Vol. 108, No. 1, 24.07.2001, p. 41-50.

Research output: Contribution to journalArticle

Ozawa, K. ; Kondo, T. ; Hori, O. ; Kitao, Y. ; Stern, David ; Eisenmenger, W. ; Ogawa, S. ; Ohshima, T. / Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 1. pp. 41-50.
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AU - Ogawa, S.

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