FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2043491040> ?p ?o ?g. }

• W2043491040 endingPage "7207" @default.
• W2043491040 startingPage "7195" @default.
• W2043491040 abstract "Prolyl-4-hydroxylase (PHD) proteins are key in sensing tissue hypoxia. In nucleus pulposus (NP) cells, our previous work demonstrated that PHD isoforms have a differential contribution in controlling hypoxia-inducible factor (HIF)-α degradation and activity. Recently we have shown that a regulatory relationship exists between PHD3 and inflammatory cytokines in NP cells. With respect to PHD2, the most abundant PHD isoform in NP cells, very little is known concerning its function and regulation under inflammatory conditions that characterize intervertebral disc degeneration. Here, we show that PHD2 is a potent regulator of the catabolic activities of TNF-α; silencing of PHD2 significantly decreased TNF-α-induced expression of catabolic markers including SDC4, MMP-3, MMP-13, and ADAMTS5, as well as several inflammatory cytokines and chemokines, while partially restoring aggrecan and collagen II expression. Use of NF-κB reporters with ShPHD2, SiHIF-1α, as well as p65−/−, PHD2−/−, and PHD3−/− cells, shows that PHD2 serves as a co-activator of NF-κB/p65 signaling in HIF-1-independent fashion. Immunoprecipitation of endogenous and exogenously expressed tagged proteins, as well as fluorescence microscopy, indicates that following TNF-α treatment, PHD2 interacts and co-localizes with p65. Conversely, loss of function experiments using lentivirally delivered Sh-p65, Sh-IKKβ, and NF-κB inhibitor confirmed that cytokine-dependent PHD2 expression in NP cells requires NF-κB signaling. These findings clearly demonstrate that PHD2 forms a regulatory circuit with TNF-α via NF-κB and thereby plays an important role in enhancing activity of this cytokine. We propose that during disc degeneration PHD2 may offer a therapeutic target to mitigate the deleterious actions of TNF-α, a key proinflammatory cytokine. Prolyl-4-hydroxylase (PHD) proteins are key in sensing tissue hypoxia. In nucleus pulposus (NP) cells, our previous work demonstrated that PHD isoforms have a differential contribution in controlling hypoxia-inducible factor (HIF)-α degradation and activity. Recently we have shown that a regulatory relationship exists between PHD3 and inflammatory cytokines in NP cells. With respect to PHD2, the most abundant PHD isoform in NP cells, very little is known concerning its function and regulation under inflammatory conditions that characterize intervertebral disc degeneration. Here, we show that PHD2 is a potent regulator of the catabolic activities of TNF-α; silencing of PHD2 significantly decreased TNF-α-induced expression of catabolic markers including SDC4, MMP-3, MMP-13, and ADAMTS5, as well as several inflammatory cytokines and chemokines, while partially restoring aggrecan and collagen II expression. Use of NF-κB reporters with ShPHD2, SiHIF-1α, as well as p65−/−, PHD2−/−, and PHD3−/− cells, shows that PHD2 serves as a co-activator of NF-κB/p65 signaling in HIF-1-independent fashion. Immunoprecipitation of endogenous and exogenously expressed tagged proteins, as well as fluorescence microscopy, indicates that following TNF-α treatment, PHD2 interacts and co-localizes with p65. Conversely, loss of function experiments using lentivirally delivered Sh-p65, Sh-IKKβ, and NF-κB inhibitor confirmed that cytokine-dependent PHD2 expression in NP cells requires NF-κB signaling. These findings clearly demonstrate that PHD2 forms a regulatory circuit with TNF-α via NF-κB and thereby plays an important role in enhancing activity of this cytokine. We propose that during disc degeneration PHD2 may offer a therapeutic target to mitigate the deleterious actions of TNF-α, a key proinflammatory cytokine." @default.
• W2043491040 created "2016-06-24" @default.
• W2043491040 creator A5012718663 @default.
• W2043491040 creator A5019521528 @default.
• W2043491040 creator A5027835055 @default.
• W2043491040 creator A5051764231 @default.
• W2043491040 creator A5077942573 @default.
• W2043491040 creator A5081676218 @default.
• W2043491040 creator A5088924669 @default.
• W2043491040 date "2015-03-01" @default.
• W2043491040 modified "2023-10-17" @default.
• W2043491040 title "Prolyl-4-hydroxylase Domain Protein 2 Controls NF-κB/p65 Transactivation and Enhances the Catabolic Effects of Inflammatory Cytokines on Cells of the Nucleus Pulposus" @default.
• W2043491040 cites W127202646 @default.
• W2043491040 cites W1453797714 @default.
• W2043491040 cites W1495830587 @default.
• W2043491040 cites W1505597474 @default.
• W2043491040 cites W1619977460 @default.
• W2043491040 cites W1964195533 @default.
• W2043491040 cites W1979264581 @default.
• W2043491040 cites W1988377666 @default.
• W2043491040 cites W1999522012 @default.
• W2043491040 cites W2014860499 @default.
• W2043491040 cites W2016160962 @default.
• W2043491040 cites W2018935238 @default.
• W2043491040 cites W2024585159 @default.
• W2043491040 cites W2029322941 @default.
• W2043491040 cites W2036852252 @default.
• W2043491040 cites W2038127811 @default.
• W2043491040 cites W2044474568 @default.
• W2043491040 cites W2049873586 @default.
• W2043491040 cites W2050573744 @default.
• W2043491040 cites W2056425530 @default.
• W2043491040 cites W2059483506 @default.
• W2043491040 cites W2068747348 @default.
• W2043491040 cites W2072526492 @default.
• W2043491040 cites W2089141914 @default.
• W2043491040 cites W2094412032 @default.
• W2043491040 cites W2096298530 @default.
• W2043491040 cites W2102471535 @default.
• W2043491040 cites W2103154710 @default.
• W2043491040 cites W2120329137 @default.
• W2043491040 cites W2120483851 @default.
• W2043491040 cites W2127562514 @default.
• W2043491040 cites W2129346144 @default.
• W2043491040 cites W2131905943 @default.
• W2043491040 cites W2138565463 @default.
• W2043491040 cites W2141918663 @default.
• W2043491040 cites W2146617670 @default.
• W2043491040 cites W2166016039 @default.
• W2043491040 cites W2332850050 @default.
• W2043491040 cites W4293765706 @default.
• W2043491040 cites W4361868163 @default.
• W2043491040 doi "https://doi.org/10.1074/jbc.m114.611483" @default.
• W2043491040 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4358139" @default.
• W2043491040 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25635047" @default.
• W2043491040 hasPublicationYear "2015" @default.
• W2043491040 type Work @default.
• W2043491040 sameAs 2043491040 @default.
• W2043491040 citedByCount "43" @default.
• W2043491040 countsByYear W20434910402015 @default.
• W2043491040 countsByYear W20434910402016 @default.
• W2043491040 countsByYear W20434910402017 @default.
• W2043491040 countsByYear W20434910402018 @default.
• W2043491040 countsByYear W20434910402019 @default.
• W2043491040 countsByYear W20434910402020 @default.
• W2043491040 countsByYear W20434910402021 @default.
• W2043491040 countsByYear W20434910402022 @default.
• W2043491040 countsByYear W20434910402023 @default.
• W2043491040 crossrefType "journal-article" @default.
• W2043491040 hasAuthorship W2043491040A5012718663 @default.
• W2043491040 hasAuthorship W2043491040A5019521528 @default.
• W2043491040 hasAuthorship W2043491040A5027835055 @default.
• W2043491040 hasAuthorship W2043491040A5051764231 @default.
• W2043491040 hasAuthorship W2043491040A5077942573 @default.
• W2043491040 hasAuthorship W2043491040A5081676218 @default.
• W2043491040 hasAuthorship W2043491040A5088924669 @default.
• W2043491040 hasBestOaLocation W20434910401 @default.
• W2043491040 hasConcept C104317684 @default.
• W2043491040 hasConcept C123298856 @default.
• W2043491040 hasConcept C1292079 @default.
• W2043491040 hasConcept C164027704 @default.
• W2043491040 hasConcept C17991360 @default.
• W2043491040 hasConcept C181199279 @default.
• W2043491040 hasConcept C185592680 @default.
• W2043491040 hasConcept C203014093 @default.
• W2043491040 hasConcept C2776914184 @default.
• W2043491040 hasConcept C2777730290 @default.
• W2043491040 hasConcept C2778690821 @default.
• W2043491040 hasConcept C2779730028 @default.
• W2043491040 hasConcept C55493867 @default.
• W2043491040 hasConcept C62478195 @default.
• W2043491040 hasConcept C71829478 @default.
• W2043491040 hasConcept C86339819 @default.
• W2043491040 hasConcept C86803240 @default.
• W2043491040 hasConcept C95444343 @default.
• W2043491040 hasConcept C96942376 @default.
• W2043491040 hasConceptScore W2043491040C104317684 @default.
• W2043491040 hasConceptScore W2043491040C123298856 @default.

• next