
<ArticleTitle>Expression of the <prot>oxygen-regulated protein</prot> <prot>ORP150</prot> accelerates wound healing by modulating intracellular <prot>VEGF</prot> transport.</ArticleTitle>
<AbstractText>Expression of angiogenic factors such as <prot>VEGF</prot> under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone <prot>oxygen-regulated protein 150</prot> (<prot>ORP150</prot>) is expressed in human wounds along with <prot>VEGF</prot>. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of <prot>ORP150</prot> in the promotion of angiogenesis. Local administration of <prot>ORP150</prot> sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased <prot>VEGF</prot> antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of <prot>ORP150</prot> expression caused retention of <prot>VEGF</prot> antigen within the endoplasmic reticulum (ER), while overexpression of <prot>ORP150</prot> promoted the secretion of <prot>VEGF</prot> into hypoxic culture supernatants. Taken together, these data suggest an important role for <prot>ORP150</prot> 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.</AbstractText>
