A short peptide derived from pigment epithelial-derived factor exhibits an angioinhibitory effect

Abstract

Background Pigment epithelial-derived factor (PEDF), a 50 kDa secreted glycoprotein, exhibits distinct effects on a range of cell types. PEDF has been shown to inhibit vascular endothelial growth factor (VEGF)-mediated angiogenesis and widely accepted as a promising agent for treatment eye diseases related to neovascularization. A pool of short peptide fragments derived from PEDF reportedly manifests angioinhibitory activity. This study aims to determine the minimal PEDF fragment which can exert the anti-VEGF effect. Methods A series of shorter synthetic peptides, derived from the 34-mer (PEDF amino acid positions Asp44-Asn77), were synthesized. An MTT assay was used to evaluate the ability of the 34-mer-derived peptides to inhibit VEGF-induced proliferation of multiple myeloma RPMI8226 cells. Cell apoptosis was monitored by annexin V-FITC staining. Western blot analysis was used to detect phosphorylated kinases, including c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and the expression of apoptosis-associated proteins, including p53, bax and caspase-3. VEGF-mediated angiogenesis of human umbilical vein endothelial cells (HUVECs), rat aortic ring and mouse cornea were used to detect the angioinhibitory activity of the PEDF-derived peptides. Results The MTT assay showed that the anti-VEGF effect of a 7-mer (Asp64-Ser70) was 1.5-fold greater than the 34-mer. In addition, massive apoptosis (37%) was induced by 7-mer treatment. The 7-mer induced JNK phosphorylation in RPMI8226 cells. Cell apoptosis and apoptosis-associated proteins induced by the 7-mer were blocked by pharmacological inhibition of JNK, but not p38 MAPK. Moreover, the 7-mer prevented VEGF-mediated angiogenesis of endothelial cells (ECs), including tube formation, aortic EC spreading and corneal neovascularization in mice. Conclusions This is the first study to show that the PEDF 7-mer peptide manifests anti-VEGF activity, further establishing its potential as an anti-angiogenic agent.

Advancements in Neovascular Ophthalmopathy: Therapeutic Strategies and Future Prospects

“…This opens up innovative therapeutic approaches for future neovascular eye diseases [172] . Additionally, PEDF-derived short synthetic peptides retain anti-angiogenic activity and may be more suitable as anti-angiogenic drugs than the full PEDF protein [173] . PEDF is currently used to treat neovascular eye diseases in various forms, including direct administration [174] , nanoparticles (such as PLGA nanospheres and liposomes) [173,175] , and viral vectors [176,177] .…”

“…Additionally, PEDF-derived short synthetic peptides retain anti-angiogenic activity and may be more suitable as anti-angiogenic drugs than the full PEDF protein [173] . PEDF is currently used to treat neovascular eye diseases in various forms, including direct administration [174] , nanoparticles (such as PLGA nanospheres and liposomes) [173,175] , and viral vectors [176,177] . Each delivery method has its advantages and should be selected based on the specific treatment scenario.…”