Endo-PDI is required for TNFα-induced angiogenesis

Camargo, Livia L; Bábelová, Andrea; Mieth, Anja; Weigert, Andreas; Mooz, Juliane; Rajalingam, Krishnaraj; Heide, Heinrich; Wittig, Ilka; Lopes, Lucia Rossetti; Brandes, Ralf P.

doi:10.1016/j.freeradbiomed.2013.09.028

Cited by 32 publications

(29 citation statements)

References 40 publications

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“…These agents induce proteins with antioxidative functions (TXNDC5), and downregulate oxidative proteins (Nox2). Thus, these findings give further support to the antioxidative function of TXNDC5 [ 47 , 48 ].…”

Section: Txndc5 Proteinsupporting

confidence: 59%

“…Ras activation induces AP-1-dependent gene expression, contributing to endothelial cell angiogenesis in response to cytokines. Despite this fact, we can infer that an increase in TXNC5 expression may contribute to the angiogenic response in cancer [ 48 ]. In addition, TXNDC5 can act as an enhancer for pro-oncogene MYC expression.…”

Section: Txndc5 In Physiology and Pathologymentioning

confidence: 99%

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TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

Horna-Terrón

Pradilla-Dieste

Sánchez-de-Diego

et al. 2014

IJMS

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Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family, acting as a chaperone of endoplasmic reticulum under not fully characterized conditions As a result, TXNDC5 interacts with many cell proteins, contributing to their proper folding and correct formation of disulfide bonds through its thioredoxin domains. Moreover, it can also work as an electron transfer reaction, recovering the functional isoform of other protein disulfide isomerases, replacing reduced glutathione in its role. Finally, it also acts as a cellular adapter, interacting with the N-terminal domain of adiponectin receptor. As can be inferred from all these functions, TXNDC5 plays an important role in cell physiology; therefore, dysregulation of its expression is associated with oxidative stress, cell ageing and a large range of pathologies such as arthritis, cancer, diabetes, neurodegenerative diseases, vitiligo and virus infections. Its implication in all these important diseases has made TXNDC5 a susceptible biomarker or even a potential pharmacological target.

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Section: Txndc5 Proteinsupporting

confidence: 59%

Section: Txndc5 In Physiology and Pathologymentioning

confidence: 99%

TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

Horna-Terrón

Pradilla-Dieste

Sánchez-de-Diego

et al. 2014

IJMS

View full text Add to dashboard Cite

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“…As such, annexin A1, a protein known to mediate VEGF-induced endothelial cell migration by regulating the formation of lamellipodia [43], is only detected in the cytosolic ASC-related fraction whereas peroxiredoxin-1, a protein known to stimulate endothelial cell proliferation and migration by interacting with toll-like receptor 4 (TLR4), is only identified in the ASC secretome [44]. Finally, in contrast to the ASC-related secretome, ASCs provide a high number of proteins implicated in the regulation of protein translation and folding, and with molecular chaperone activity such as heat shock protein (HSP)70-1A and protein disulfide isomerase (PDI) known to be involved in-vivo angiogenesis [45, 46]. Overall, our observations suggest the existence of a synergistic and coordinated protein network in the ASC interactome involved in angiogenesis modulation.…”

Section: Discussionmentioning

confidence: 99%

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

et al. 2017

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BackgroundMyocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI.MethodsPig subcutaneous adipose tissue ASCs were isolated, expanded and GFP-labeled. ASC angiogenic function was assessed by the in-vivo chick chorioallantoic membrane (CAM) model. Pigs underwent MI induction and 7 days after were randomized to receive: allogenic ASCs (intracoronary infusion); conditioned media (CM; intravenous infusion); ASCs + CM; or PBS/placebo (control). Cardiac damage and function were monitored by 3-T cardiac magnetic resonance imaging upon infusion (baseline CMR) and 1 and 3 weeks thereafter. We assessed in the myocardium: microvessel density; angiogenic markers (CD105, CD31, TF, VEGFR2, VEGFR1, vWF, eNOS, CD62); collagen deposition; and reparative fibrosis (TGFβ/TβRII/collagen). Differential proteomics of ASCs and CM was performed to characterize the ASC protein signature.ResultsCAM indicated a significant ASC proangiogenic capacity. In pigs after MI, only PBS/placebo animals displayed an impaired cardiac function 3 weeks after infusion (p < 0.05 vs baseline). Administration of ASCs + CM significantly enhanced neovessel formation and favored cardiac repair post MI (p < 0.05 vs the other groups). Molecular markers of angiogenesis were significantly upregulated both at transcriptional and protein levels (p < 0.05). The in-silico bioinformatics analysis of the ASC and CM proteome (interactome) indicated activation of a coordinated protein network involved in the formation of microvessels and the resolution of rarefaction.ConclusionCoadministration of allogenic ASCs and their CM synergistically contribute to the neovascularization of the infarcted myocardium through a coordinated upregulation of the proangiogenic protein interactome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0509-2) contains supplementary material, which is available to authorized users.

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“…[69] Many other factors are known to regulate MMP-9 besides TNF-α, including the inflammatory cytokines IL-1β and IL-1α. [26, 70, 71] In fact, in a pivotal study by Bond et al, IL-1β was proven to be a more potent promoter of MMP-9 than TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels

et al. 2014

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Peripheral artery disease (PAD) is characterized by vessel occlusion and ischemia in the limbs. Treatment for PAD with surgical interventions has been showing limited success. Moreover, recent clinical trials with treatment of angiogenic growth factors proved ineffective as increased angiogenesis triggered severe inflammation in a proportionally coupled fashion. Hence, the overarching goal of this research was to address this issue by developing a biomaterial system that enables controlled, dual delivery of pro-angiogenic C16 and anti-inflammatory Ac-SDKP peptides in a minimally-invasive way. To achieve the goal, a peptide-loaded injectable microgel system was developed and tested in a mouse model of PAD. When delivered through multiple, low volume injections, the combination of C16 and Ac-SDKP peptides promoted angiogenesis, muscle regeneration, and perfusion recovery, while minimizing detrimental inflammation. Additionally, this peptide combination regulated inflammatory TNF-α pathways independently of MMP-9 mediated pathways of angiogenesis in vitro, suggesting a potential mechanism by which angiogenic and inflammatory responses can be uncoupled in the context of PAD. This study demonstrates a translatable potential of the dual peptide-loaded injectable microgel system for PAD treatment.

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Endo-PDI is required for TNFα-induced angiogenesis

Cited by 32 publications

References 40 publications

TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

TXNDC5, a Newly Discovered Disulfide Isomerase with a Key Role in Cell Physiology and Pathology

Allogenic adipose-derived stem cell therapy overcomes ischemia-induced microvessel rarefaction in the myocardium: systems biology study

Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels

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