Identification of Downstream Mechanisms Involved in PEDF’s Activity in the Retina by Large Scale Gene Expression Profiling

Tombran-Tink, Joyce; Lara, Nuria; Chappa, A.; Tink, A.R.; Johnson, Lincoln V.; Staples, Michelle K

doi:10.1007/978-1-4615-0067-4_39

Cited by 2 publications

(1 citation statement)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A fourth way by which PEDF could block endothelial cell growth and reduce angiogenesis is by regulating the MAPK signaling module. In bovine retinal endothelial cells this could occur in two ways: by decreasing the transcription of MAP kinase kinase 1(MAPKK1) and by altering VEGF-induced phosphorylation of ERK1/2 (98,106). The regulation of ERK1/2 phosphorylation by PEDF however, varies according to the growth conditions under which endothelial cells are exposed (98).…”

Section: Angiogenic Signalingmentioning

confidence: 99%

The neuroprotective and angiogenesis inhibitory serpin, PEDF: new insights into phylogeny, function, and signaling

Tombran-Tink¹

2005

Front Biosci

View full text Add to dashboard Cite

Pigment Epithelial-Derived Factor (PEDF) is a non inhibitory serpin with neuroprotective and antiangiogenic actions. It is a potent and broadly acting neurotrophic factor that protects neurons from many regions of the CNS against a wide range of neurodegenerative insults including glutamate toxicity and oxidative stress. PEDF also functions as a natural inhibitor of angiogenesis, targeting the growth of only new vessels. The 50 kD protein is encoded by a single gene that shows strong conservation across phyla from fish to mammals. Two specific domains on the PEDF protein interact with extracellular matrix components and may mediate some of the biological actions of this protein. The transducers through which PEDF signals neurons and endothelial cells are defined and involves major pathways including Akt/NFkB , MAPK, and the caspases. PEDF is widely expressed in the nervous system and in most tissues of the body. A significant amount of the protein is found in the cerebral spinal fluid and circulating plasma as well. Therapeutic administration of the soluble protein or viral-mediated transfer of the gene in experimental in vivo models suggests that PEDF is an excellent pharmacological tool for slowing the progression of a range of neurodegenerative diseases and those pathologies associated with abnormal vessel growth in the eye and metastatic cancers of various tissues.

show abstract

Section: Angiogenic Signalingmentioning

confidence: 99%