Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

Shields, Kristin; Panzhinskiy, Evgeniy; Burns, Nana; Zawada, W. Michael; Das, Mita

doi:10.1016/j.ajpath.2010.11.025

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…VEGF is a known target of p38 MAPK signalling (Demyanets et al 2011; Hiratsuka et al 2011; Shields et al 2011) and is upregulated in fibrotic lungs (Fehrenbach et al 1999; Meyer et al 2000; Steurer et al 2007). Since p38 MAPK was activated by SWCNTs, we tested the effect of SWCNTs on VEGF level.…”

Section: Resultsmentioning

confidence: 99%

Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses

et al. 2012

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Single-walled carbon nanotubes (SWCNTs) are fibrous nanoparticles that are being used widely for various applications including drug delivery. SWCNTs are currently under special attention for possible cytotoxicity. Recent reports suggest that exposure to nanoparticles leads to pulmonary fibrosis. We report that SWCNT-mediated interplay of fibrogenic and angiogenic regulators leads to increased angiogenesis, which is a novel finding that furthers the understanding of SWCNT-induced cytotoxicity. SWCNTs induce fibrogenesis through reactive oxygen species-regulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Activation of p38 MAPK by SWCNTs led to the induction of transforming growth factor (TGF)-β1 as well as vascular endothelial growth factor (VEGF). Both TGF-β1 and VEGF contributed significantly to the fibroproliferative and collagen-inducing effects of SWCNTs. Interestingly, a positive feedback loop was observed between TGF-β1 and VEGF. This interplay of fibrogenic and angiogenic mediators led to increased angiogenesis in response to SWCNTs. Overall this study reveals key signalling molecules involved in SWCNT-induced fibrogenesis and angiogenesis.

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Section: Resultsmentioning

confidence: 99%

Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses

et al. 2012

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“…Cell free protein synthesis (CFPS) has shown its importance for pharmaceutical protein production, including the industrial production of a commercial protein drug (rhGM-CSF) 15 . However, this product was still purified using traditional methods, such as weak anion exchange chromatography, followed by filtration and several size exclusion chromatography steps, with all their problems as stated before.…”

Section: Introductionmentioning

confidence: 99%

Accelerated pharmaceutical protein development with integrated cell free expression, purification, and bioconjugation

Richardson

Itkonen

Nievas

et al. 2018

Sci Rep

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The use of living cells for the synthesis of pharmaceutical proteins, though state-of-the-art, is hindered by its lengthy process comprising of many steps that may affect the protein’s stability and activity. We aimed to integrate protein expression, purification, and bioconjugation in small volumes coupled with cell free protein synthesis for the target protein, ciliary neurotrophic factor. Split-intein mediated capture by use of capture peptides onto a solid surface was efficient at 89–93%. Proof-of-principle of light triggered release was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA). The latter was more efficient, but more time consuming. Light triggered release was clearly demonstrated. Moreover, we transferred biotin from the capture peptide to the target protein without further purification steps. Finally, the target protein was released in a buffer-volume and composition of our choice, omitting the need for protein concentration or changing the buffer. Split-intein mediated capture, protein trans splicing followed by light triggered release, and bioconjugation for proteins synthesized in cell free systems might be performed in an integrated workflow resulting in the fast production of the target protein.

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“…DUSP1 is ubiquitously expressed in the organism and it is known to bind p38MAPK, JNK or ERK depending on the cell status [26] , [27] . DUSP1 expression is strongly upregulated upon several stimuli such as oxidative stress, hypoxia, growth factors, glucocorticoids, heat shock and UV [28] , [29] , [30] , [31] , [32] . DUSP1 is tightly regulated at transcriptional, translational and post-translational levels.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the Cellular Phosphatase DUSP1 in Vaccinia Virus Infection

et al. 2013

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Poxviruses encode a large variety of proteins that mimic, block or enhance host cell signaling pathways on their own benefit. It has been reported that mitogen-activated protein kinases (MAPKs) are specifically upregulated during vaccinia virus (VACV) infection. Here, we have evaluated the role of the MAPK negative regulator dual specificity phosphatase 1 (DUSP1) in the infection of VACV. We demonstrated that DUSP1 expression is enhanced upon infection with the replicative WR virus and with the attenuated VACV viruses MVA and NYVAC. This upregulation is dependent on early viral gene expression. In the absence of DUSP1 in cultured cells, there is an increased activation of its molecular targets JNK and ERK and an enhanced WR replication. Moreover, DUSP1 knock-out (KO) mice are more susceptible to WR infection as a result of enhanced virus replication in the lungs. Significantly, MVA, which is known to produce non-permissive infections in most mammalian cell lines, is able to grow in DUSP1 KO immortalized murine embryo fibroblasts (MEFs). By confocal and electron microscopy assays, we showed that in the absence of DUSP1 MVA morphogenesis is similar as in permissive cell lines and demonstrated that DUSP1 is involved at the stage of transition between IVN and MV in VACV morphogenesis. In addition, we have observed that the secretion of pro-inflammatory cytokines at early times post-infection in KO mice infected with MVA and NYVAC is increased and that the adaptive immune response is enhanced in comparison with WT-infected mice. Altogether, these findings reveal that DUSP1 is involved in the replication and host range of VACV and in the regulation of host immune responses through the modulation of MAPKs. Thus, in this study we demonstrate that DUSP1 is actively involved in the antiviral host defense mechanism against a poxvirus infection.

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Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

Cited by 12 publications

References 42 publications

Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses

Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses

Accelerated pharmaceutical protein development with integrated cell free expression, purification, and bioconjugation

Involvement of the Cellular Phosphatase DUSP1 in Vaccinia Virus Infection

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