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• W2346951597 abstract "Urokinase-type plasminogen activator (uPA) regulates angiogenesis and vascular permeability through proteolytic degradation of extracellular matrix and intracellular signaling initiated upon its binding to uPAR/CD87 and other cell surface receptors. Here, we describe an additional mechanism by which uPA regulates angiogenesis. Ex vivo VEGF-induced vascular sprouting from Matrigel-embedded aortic rings isolated from uPA knock-out (uPA−/−) mice was impaired compared with vessels emanating from wild-type mice. Endothelial cells isolated from uPA−/− mice show less proliferation and migration in response to VEGF than their wild type counterparts or uPA−/− endothelial cells in which expression of wild type uPA had been restored. We reported previously that uPA is transported from cell surface receptors to nuclei through a mechanism that requires its kringle domain. Intranuclear uPA modulates gene transcription by binding to a subset of transcription factors. Here we report that wild type single-chain uPA, but not uPA variants incapable of nuclear transport, increases the expression of cell surface VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) by translocating to the nuclei of ECs. Intranuclear single-chain uPA binds directly to and interferes with the function of the transcription factor hematopoietically expressed homeodomain protein or proline-rich homeodomain protein (HHEX/PRH), which thereby lose their physiologic capacity to repress the activity of vehgr1 and vegfr2 gene promoters. These studies identify uPA-dependent de-repression of vegfr1 and vegfr2 gene transcription through binding to HHEX/PRH as a novel mechanism by which uPA mediates the pro-angiogenic effects of VEGF and identifies a potential new target for control of pathologic angiogenesis. Urokinase-type plasminogen activator (uPA) regulates angiogenesis and vascular permeability through proteolytic degradation of extracellular matrix and intracellular signaling initiated upon its binding to uPAR/CD87 and other cell surface receptors. Here, we describe an additional mechanism by which uPA regulates angiogenesis. Ex vivo VEGF-induced vascular sprouting from Matrigel-embedded aortic rings isolated from uPA knock-out (uPA−/−) mice was impaired compared with vessels emanating from wild-type mice. Endothelial cells isolated from uPA−/− mice show less proliferation and migration in response to VEGF than their wild type counterparts or uPA−/− endothelial cells in which expression of wild type uPA had been restored. We reported previously that uPA is transported from cell surface receptors to nuclei through a mechanism that requires its kringle domain. Intranuclear uPA modulates gene transcription by binding to a subset of transcription factors. Here we report that wild type single-chain uPA, but not uPA variants incapable of nuclear transport, increases the expression of cell surface VEGF receptor 1 (VEGFR1) and VEGF receptor 2 (VEGFR2) by translocating to the nuclei of ECs. Intranuclear single-chain uPA binds directly to and interferes with the function of the transcription factor hematopoietically expressed homeodomain protein or proline-rich homeodomain protein (HHEX/PRH), which thereby lose their physiologic capacity to repress the activity of vehgr1 and vegfr2 gene promoters. These studies identify uPA-dependent de-repression of vegfr1 and vegfr2 gene transcription through binding to HHEX/PRH as a novel mechanism by which uPA mediates the pro-angiogenic effects of VEGF and identifies a potential new target for control of pathologic angiogenesis." @default.
• W2346951597 created "2016-06-24" @default.
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• W2346951597 date "2016-07-01" @default.
• W2346951597 modified "2023-10-10" @default.
• W2346951597 title "Urokinase-type Plasminogen Activator (uPA) Promotes Angiogenesis by Attenuating Proline-rich Homeodomain Protein (PRH) Transcription Factor Activity and De-repressing Vascular Endothelial Growth Factor (VEGF) Receptor Expression" @default.
• W2346951597 cites W130026199 @default.
• W2346951597 cites W1507538406 @default.
• W2346951597 cites W1529390136 @default.
• W2346951597 cites W1546092720 @default.
• W2346951597 cites W1557058411 @default.
• W2346951597 cites W1560554297 @default.
• W2346951597 cites W1576290062 @default.
• W2346951597 cites W1584486859 @default.
• W2346951597 cites W1597299868 @default.
• W2346951597 cites W164884231 @default.
• W2346951597 cites W1963621811 @default.
• W2346951597 cites W1965286948 @default.
• W2346951597 cites W1971717022 @default.
• W2346951597 cites W1980609283 @default.
• W2346951597 cites W1985804036 @default.
• W2346951597 cites W1986308750 @default.
• W2346951597 cites W1988376520 @default.
• W2346951597 cites W1988710007 @default.
• W2346951597 cites W1988750485 @default.
• W2346951597 cites W1989850563 @default.
• W2346951597 cites W1990450608 @default.
• W2346951597 cites W1991463736 @default.
• W2346951597 cites W1996092483 @default.
• W2346951597 cites W2010781359 @default.
• W2346951597 cites W2011936885 @default.
• W2346951597 cites W2024327925 @default.
• W2346951597 cites W2026803058 @default.
• W2346951597 cites W2030459003 @default.
• W2346951597 cites W2033535700 @default.
• W2346951597 cites W2035484369 @default.
• W2346951597 cites W2037107824 @default.
• W2346951597 cites W2039971642 @default.
• W2346951597 cites W2042720684 @default.
• W2346951597 cites W2045747902 @default.
• W2346951597 cites W2046633166 @default.
• W2346951597 cites W2047561204 @default.
• W2346951597 cites W2055114143 @default.
• W2346951597 cites W2056146626 @default.
• W2346951597 cites W2059790790 @default.
• W2346951597 cites W2064758160 @default.
• W2346951597 cites W2066071406 @default.
• W2346951597 cites W2066456560 @default.
• W2346951597 cites W2067158497 @default.
• W2346951597 cites W2067680822 @default.
• W2346951597 cites W2072304034 @default.
• W2346951597 cites W2073960709 @default.
• W2346951597 cites W2076496958 @default.
• W2346951597 cites W2090154599 @default.
• W2346951597 cites W2090275556 @default.
• W2346951597 cites W2091774189 @default.
• W2346951597 cites W2095445691 @default.
• W2346951597 cites W2095498651 @default.
• W2346951597 cites W2096487443 @default.
• W2346951597 cites W2100233791 @default.
• W2346951597 cites W2100585067 @default.
• W2346951597 cites W2101564903 @default.
• W2346951597 cites W2103694989 @default.
• W2346951597 cites W2104532221 @default.
• W2346951597 cites W2105541231 @default.
• W2346951597 cites W2109272075 @default.
• W2346951597 cites W2111642677 @default.
• W2346951597 cites W2115396092 @default.
• W2346951597 cites W2115919687 @default.
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• W2346951597 cites W2130389715 @default.
• W2346951597 cites W2131420129 @default.
• W2346951597 cites W2137029911 @default.
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• W2346951597 doi "https://doi.org/10.1074/jbc.m115.678490" @default.
• W2346951597 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4946921" @default.
• W2346951597 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27151212" @default.
• W2346951597 hasPublicationYear "2016" @default.
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