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Publication : Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration.

First Author  He C Year  2014
Journal  Proc Natl Acad Sci U S A Volume  111
Issue  41 Pages  14806-11
PubMed ID  25267616 Mgi Jnum  J:216447
Mgi Id  MGI:5608823 Doi  10.1073/pnas.1404140111
Citation  He C, et al. (2014) Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration. Proc Natl Acad Sci U S A 111(41):14806-11
abstractText  Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-beta and PDGFR-alpha, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
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