PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells

Ho, Tzyy‐Chang; Chen, S.-L.; Yang, Yuh‐Cheng; Liao, Ching‐Len; Cheng, Huey-Chuan; Tsao, Yeou‐Ping

doi:10.1016/j.cardiores.2007.06.032

Cited by 119 publications

(87 citation statements)

References 35 publications

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“…12 We have recently shown that PEDF induces PPAR␥ expression in endothelial cells and that this action is responsible for the anti-angiogenesis action of PEDF. 14,15 Whether PEDF induces PPAR␥ in HSCs and affects the process of liver cirrhosis remains to be determined.…”

mentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Chen

Shih

et al. 2010

The American Journal of Pathology

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The liver is the major site of pigment epithelium-derived factor (PEDF) synthesis. Recent evidence suggests a protective role of PEDF in liver cirrhosis. In the present study, immunohistochemical analyses revealed lower PEDF levels in liver tissues of patients with cirrhosis and in animals with chemically induced liver fibrosis. Delivery of the PEDF gene into liver cells produced local PEDF synthesis and ameliorated liver fibrosis in animals treated with either carbon tetrachloride or thioacetamide. In addition, suppression of peroxisome proliferator-activated receptor gamma expression, as well as nuclear translocation of nuclear factorkappa B was found in hepatic stellate cells (HSCs) from fibrotic livers, and both changes were reversed by PEDF gene delivery. In culture-activated HSCs, PEDF, through the induction of peroxisome proliferator-activated receptor gamma, reduced the activity of nuclear factorkappa B and prevented the nuclear localization of JunD. In conclusion, our observations that PEDF levels are reduced during liver cirrhosis and that PEDF gene delivery ameliorates cirrhosis suggest that PEDF is an intrinsic protector against liver cirrhosis. Direct inactivation of HSCs and the induction of apoptosis of activated HSCs may be two of the mechanisms by which PEDF suppresses liver cirrhosis. (Am J Pathol

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mentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Chen

Shih

et al. 2010

The American Journal of Pathology

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“…PEDF accumulates in the vitreous humor and is also expressed in different adult tissues (Tombran-Tink et al, 1991). Addition of PEDF to the cultured HUVECs increased the number of TUNEL positive cells suggesting apoptotic mode of action of PEDF and thus, possibly preventing EC response to ischemia in-vivo (Ho et al, 2007). The levels of PEDF were found to be decreased in Bruch membrane with progression of AMD and concomitant increase in VEGF levels were also identified with decrease in PEDF levels (Bhutto et al, 2008).…”

Section: Pigment Epithelium Derived Factor (Pedf)mentioning

confidence: 94%

Regulation of Angiogenesis in Choroidal Neovascularization of Age Related Macular Degeneration by Endogenous Angioinhibitors

Gunda¹,

Sudhakar²

2012

Advances in Ophthalmology

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“…Introducing exogenous full-length or fragments of PEDF enables it/them to target endothelial cells by inhibiting their proliferation and migration into the bloodstream through apoptosis of endothelial cells recruited by the tumour [16,23,24]. This method does not only prevent the expansion of blood vessels to the tumour but also inhibits tumour growth by restricting the tumour's supply of nutrients and oxygen [16].…”

Section: Pedf: An Antiangiogenic and Anticancer Agentmentioning

confidence: 99%

“…DHA's apoptotic role in tumour cells) and antiangiogenic functions (e.g. PLA2 mediating PPAR-gamma ligands to activate the PPAR-gamma receptor in vascular endothelial cells) [23,37].…”

Section: Pedf Receptorsmentioning

confidence: 99%

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Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: a patent perspective

Manalo

Choong

Becerra

et al. 2011

Expert Opinion on Therapeutic Patents

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Background-Traditional forms of cancer therapy, which includes chemotherapy, have largely been overhauled due to the significant degree of toxicity they pose to normal, otherwise healthy tissue. It is hoped that use of biological agents, most of which are endogenously present in the body, will lead to safer treatment outcomes, without sacrificing efficacy.Objective-The finding that PEDF, a naturally-occurring protein, was a potent angiogenesis inhibitor became the basis for studying the role of PEDF in tumours that are highly resistant to chemotherapy. The determination of the direct role of PEDF against cancer paved the way for understanding and developing PEDF as a novel drug. This review focuses on the patent applications behind testing the anticancer therapeutic effect of PEDF via its receptors as an antiangiogenic agent and as a direct anticancer agent.Conclusions-The majority of the PEDF patents describe its and/or its fragments' antiangiogenic ability and the usage of recombinant vectors as the mode of treatment delivery. Declaration of interestThe authors declare no conflict of interest and have received no payment in preparation for this manuscript. PEDF's therapeutic potential against different diseases and the discovery of its receptors opens possibilities for improving PEDF-based peptide design and drug delivery modes. NIH Public Access

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PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells

Cited by 119 publications

References 35 publications

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Regulation of Angiogenesis in Choroidal Neovascularization of Age Related Macular Degeneration by Endogenous Angioinhibitors

Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: a patent perspective

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