| RRC ID |
4778
|
| Author |
Ozawa K, Kondo T, Hori O, Kitao Y, Stern DM, Eisenmenger W, Ogawa S, Ohshima T.
|
| Title |
Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport.
|
| Journal |
J Clin Invest
|
| 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.
|
| Volume |
108(1)
|
| Pages |
41-50
|
| Published |
2001-7-1
|
| DOI |
10.1172/JCI11772
|
| PMID |
11435456
|
| PMC |
PMC209338
|
| MeSH |
Adenoviridae / genetics
Animals
Cell Hypoxia / physiology*
Cells, Cultured
Culture Media, Conditioned
DNA-Binding Proteins / physiology
Diabetes Complications
Diabetes Mellitus / genetics
Endoplasmic Reticulum / metabolism
Endothelial Growth Factors / biosynthesis
Endothelial Growth Factors / genetics
Endothelial Growth Factors / physiology*
Endothelium, Vascular / cytology
Endothelium, Vascular / metabolism
Female
Fibroblast Growth Factor 2 / physiology
Gene Expression Regulation / drug effects
Genetic Therapy
Genetic Vectors / administration & dosage
Genetic Vectors / genetics
HSP70 Heat-Shock Proteins
Humans
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Lymphokines / biosynthesis
Lymphokines / genetics
Lymphokines / physiology*
Macrophages / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Molecular Chaperones / physiology*
Neovascularization, Pathologic / physiopathology
Neovascularization, Physiologic / physiology*
Nuclear Proteins / physiology
Oxygen / pharmacology
Protein Transport
Proteins / genetics
Proteins / physiology*
RNA, Antisense / pharmacology
RNA, Messenger / metabolism
Rats
Recombinant Fusion Proteins / physiology
Single-Blind Method
Skin / blood supply
Skin / injuries
Transcription Factors*
Transforming Growth Factor beta / physiology
Transforming Growth Factor beta1
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Wound Healing / physiology
|
| IF |
11.864
|
| Times Cited |
118
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| Resource |
| DNA material |
AxCALacZ (RDB01745) Ax1 CA gfp (RDB01727) |
