Regulation of factors controlling angiogenesis in liver development: a role for PEDF in the formation and maintenance of normal vasculature

Sawant, S.; Aparicio, Samuel; Tink, A.R.; Lara, Nuria; Barnstable, Colin J.; Tombran-Tink, Joyce

doi:10.1016/j.bbrc.2004.10.041

Cited by 56 publications

(32 citation statements)

References 23 publications

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“…PEDF is produced in most mammalian tissues (8,15,19,56,68). Among them, the liver and kidney are considered the major sources of PEDF in the circulation (43).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Park

Lee

Zhang

et al. 2011

Molecular and Cellular Biology

118

129

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Wnt signaling is known to regulate multiple processes including angiogenesis, inflammation, and fibrosis. Here, we identified a novel inhibitor of the Wnt pathway, pigment epithelium-derived factor (PEDF), a multifunctional serine proteinase inhibitor. Both overexpression of PEDF in transgenic mice and administration of PEDF protein attenuated Wnt signaling induced by retinal ischemia. Furthermore, PEDF knockdown by small interfering RNA (siRNA) and PEDF knockout in PEDF ؊/؊ mice induced activation of Wnt signaling. PEDF bound to LRP6, a Wnt coreceptor, with high affinity (K d [dissociation constant] of 3.7 nM) and blocked the Wnt signaling induced by Wnt ligand. The physical interaction of PEDF with LRP6 was confirmed by a coprecipitation assay, which showed that PEDF bound to LRP6 at the E1E2 domain. In addition, binding of PEDF to LRP6 blocked Wnt ligand-induced LRP6-Frizzled receptor dimerization, an essential step in Wnt signaling. These results suggest that PEDF is an endogenous antagonist of LRP6, and blocking Wnt signaling may represent a novel mechanism for its protective effects against diabetic retinopathy.

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“…PEDF is produced in most mammalian tissues (8,15,19,56,68). Among them, the liver and kidney are considered the major sources of PEDF in the circulation (43).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Park

Lee

Zhang

et al. 2011

Molecular and Cellular Biology

118

129

View full text Add to dashboard Cite

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“…PEDF is naturally expressed by most organs of the human body, including the eye [23], liver [24], brain [25], spinal cord [26], pancreas, prostate, plasma [27], bone [28], lung and heart [29], and it is released from most cell types as an extracellular diffusible and circulating glycoprotein. PEDF has potent anti-inflammatory, anti-oxidant and anti-thrombotic effects and inhibits EC injury, suggesting its involvement in ACS.…”

Section: Discussionmentioning

confidence: 99%

The Association Study of Plasma Levels of Pigment Epithelium-Derived Factor with Acute Coronary Syndrome in the Chinese Han Population

et al. 2013

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Objects: To investigate the relationship between plasma levels of pigment epithelium-derived factor (PEDF) and acute coronary syndrome (ACS) in the Chinese Han population. Methods: Plasma PEDF levels were measured in 200 consecutive ACS patients and 160 age- and sex-matched healthy control subjects. Logistic regression analysis was performed to determine whether PEDF was an independently protective factor against ACS. All ACS patients were followed up for 6 months and the short-term major adverse cardiovascular events (MACE) were obtained: cardiac death and recurrent angina. Results: The ACS patients showed notably lower plasma PEDF levels relative to the control group (7.31 ± 2.21 vs. 8.44 ± 2.13 μg/ml, respectively, p = 0.001). Logistic regression analysis revealed that PEDF had a significant protective effect against ACS (OR = 0.76, 95% CI 0.623-0.935, p = 0.01). After 6 months of follow-up, we found that the mean PEDF concentration of the patients with short-term MACE was lower than the patients without (6.05 ± 2.18 vs. 7.52 ± 2.07 µg/ml, p = 0.031). The Kaplan-Meier survival curves suggested that patients with plasma PEDF levels <7.00 µg/ml showed a lower survival trend than those in the higher group, but the difference was not significant (p = 0.477). Conclusions: Our study indicates that plasma PEDF levels are significantly lower in ACS patients than in controls, and lower PEDF levels are further associated with adverse cardiac outcomes after ACS.

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“…PEDF is a 50 kD protein that is a potent inhibitor of angiogenesis (20) and is expressed at high levels in normal hepatocytes and liver parenchymal cells (21,22). Purified recombinant PEDF protein has been shown to inhibit the effects of several inducers of angiogenesis on endothelial cells including, VEGF, aFGF (fibroblast growth factor), bFGF, IL-8, lysophosphatidic acid, and platelet-derived growth factor (20).…”

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confidence: 99%