Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site.
Vascular permeability plays a key role in a wide array of life-threatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability.
Liu
Hua
H
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21287-8984, USA.
Ren
Jian-Guo
JG
Cooper
William L
WL
Hawkins
Charles E
CE
Cowan
Mitra R
MR
Tong
Patrick Y
PY
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002199:Capillary Permeability / Q000502:physiology*; D002460:Cell Line; D005136:Eye Proteins; D005451:Fluorescein Angiography; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012171:Retinal Vessels / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D011994:Recombinant Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor