VEGF-A Links Angiogenesis and Inflammation in Inflammatory Bowel Disease Pathogenesis

Scaldaferri, Franco; Vetrano, Stefania; Sans, Miquel; Arena, Vincenzo; Straface, Giuseppe; Stigliano, Egidio; Repici, Alessandro; Sturm, Andreas; Malesci, Alberto; Panés, Julián; Ylä‐Herttuala, Seppo; Fiocchi, Claudio; Danese, Silvio

doi:10.1053/j.gastro.2008.09.064

Cited by 290 publications

(267 citation statements)

References 52 publications

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“…No significant difference was found in PAR-1 expression on ECs between NL subjects and patients with CD, whereas PAR-1 was significantly down-regulated in patients with UC compared with NL subjects and patients with CD. We quantified protein expression in the tissue by a semiquantitative score (10,12). We found a significant decrease in the expression of epithelial EPCR in tissue samples from patients with UC (0.8 ± 0.2) and those with CD (0.8 ± 0.2) compared with mucosa from normal individuals (2.7 ± 0.1) (P < 0.001).…”

Section: Resultsmentioning

confidence: 93%

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Vetrano

Ploplis

Sala

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The protein C (PC) pathway is a well-characterized coagulation system. Endothelial PC receptors and thrombomodulin mediate the conversion of PC to its activated form, a potent anticoagulant and anti-inflammatory molecule. Here we show that the PC pathway is expressed on intestinal epithelial cells. The epithelial expression of PC and endothelial PC receptor is down-regulated In patients with inflammatory bowel disease. PC −/− /PC(Tg) mice, expressing only 3% of WT PC, developed spontaneous intestinal inflammation and were prone to severe experimental colitis. These mice also demonstrated spontaneous elevated production of inflammatory cytokines and increased intestinal permeability. Structural analysis of epithelial tight junction molecules revealed that lack of PC leads to decreased JAM-A and claudin-3 expression and an altered pattern of ZO-1 expression. In vitro, treatment of epithelial cells with activated PC led to protection of tight junction disruption induced by TNF-α, and in vivo, topical treatment with activated PC led to mucosal healing and amelioration of colitis. Taken together, these findings demonstrate that the PC pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function.

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Section: Resultsmentioning

confidence: 93%

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Vetrano

Ploplis

Sala

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…On the other hand, the PR diet, like AB, downregulated the CCL20 chemokine, preventing the effect observed in a variety of inflammatory disorders (Sibartie et al, 2009). These data were reinforced by the reduction of the expression of IFRD, an IFN-inducible gene (Mulder et al, 2009), of TFF3, a gene strongly induced after mucosal injury (Taupin et al, 2001) and of VEGF-A, a target gene involved in the induction of mucosal inflammation (Scaldaferri et al, 2009). These results indicated the role of Sc in maintaining mucosal homeostasis during ETEC infection.…”

Section: Discussionmentioning

confidence: 98%

Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4

Trevisi

Latorre

Priori

et al. 2017

Animal

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The ability of live yeasts to modulate pig intestinal cell signals in response to infection with Escherichia coli F4ac (ETEC) has not been studied in-depth. The aim of this trial was to evaluate the effect of Saccharomyces cerevisiae CNCM I-4407 (Sc), supplied at different times, on the transcriptome profile of the jejunal mucosa of pigs 24 h after infection with ETEC. In total, 20 piglets selected to be ETEC-susceptible were weaned at 24 days of age (day 0) and allotted by litter to one of following groups: control (CO), CO + colistin (AB), CO + 5 × 10 10 colony-forming unit (CFU) Sc/kg feed, from day 0 (PR) and CO + 5 × 10 10 CFU Sc/kg feed from day 7 (CM). On day 7, the pigs were orally challenged with ETEC and were slaughtered 24 h later after blood sampling for haptoglobin (Hp) and C-reactive protein (CRP) determination. The jejunal mucosa was sampled (1) for morphometry; (2) for quantification of proliferation, apoptosis and zonula occludens (ZO-1); (3) to carry out the microarray analysis. A functional analysis was carried out using Gene Set Enrichment Analysis. The normalized enrichment score (NES) was calculated for each gene set, and statistical significance was defined when the False Discovery Rate % was <25 and P-values of NES were <0.05. The blood concentration of CRP and Hp, and the score for ZO-1 integrity on the jejunal villi did not differ between groups. The intestinal crypts were deeper in the AB (P = 0.05) and the yeast groups (P < 0.05) than in the CO group. Antibiotic treatment increased the number of mitotic cells in intestinal villi as compared with the control group (P < 0.05). The PR group tended to increase the mitotic cells in villi and crypts and tended to reduce the cells in apoptosis as compared with the CM group. The transcriptome profiles of the AB and PR groups were similar. In both groups, the gene sets involved in mitosis and in mitochondria development ranked the highest, whereas in the CO group, the gene sets related to cell junction and anion channels were affected. In the CM group, the gene sets linked to the metabolic process, and transcription ranked the highest; a gene set linked with a negative effect on growth was also affected. In conclusion, the constant supplementation in the feed with the strain of yeast tested was effective in counteracting the detrimental effect of ETEC infection in susceptible pigs limits the early activation of the gene sets related to the impairment of the jejunal mucosa.

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“…Thus, it appears that inflammatory stimuli propagate circles of interactions of Opn and integrin α9. It has to be emphasized that there are other candidate ligands of integrin α9, such as TN-C, vascular cell adhesion molecule-1, and VEGF-A (19,(82)(83)(84), some of which are overexpressed in the colitic microenvironment (85,86). It is unknown whether interactions of these molecules with integrin α9 on CD103 − DCs enhance or restrain the described proinflammatory function of Opn.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin expression by CD103⁻dendritic cells drives intestinal inflammation

Kourepini

Aggelakopoulou

Alissafi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Intestinal CD103 − dendritic cells (DCs) are pathogenic for colitis. Unveiling molecular mechanisms that render these cells proinflammatory is important for the design of specific immunotherapies. In this report, we demonstrated that mesenteric lymph node CD103 − DCs express, among other proinflammatory cytokines, high levels of osteopontin (Opn) during experimental colitis. Opn expression by CD103 − DCs was crucial for their immune profile and pathogenicity, including induction of T helper (Th) 1 and Th17 cell responses. Adoptive transfer of Opn-deficient CD103 − DCs resulted in attenuated colitis in comparison to transfer of WT CD103 − DCs, whereas transgenic CD103 − DCs that overexpress Opn were highly pathogenic in vivo. Neutralization of secreted Opn expressed exclusively by CD103 − DCs restrained disease severity. Also, Opn deficiency resulted in milder disease, whereas systemic neutralization of secreted Opn was therapeutic. We determined a specific domain of the Opn protein responsible for its CD103 − DC-mediated proinflammatory effect. We demonstrated that disrupting the interaction of this Opn domain with integrin α9, overexpressed on colitic CD103 − DCs, suppressed the inflammatory potential of these cells in vitro and in vivo. These results add unique insight into the biology of CD103 − DCs and their function during inflammatory bowel disease.

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VEGF-A Links Angiogenesis and Inflammation in Inflammatory Bowel Disease Pathogenesis

Cited by 290 publications

References 52 publications

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4

Osteopontin expression by CD103⁻dendritic cells drives intestinal inflammation

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VEGF-A Links Angiogenesis and Inflammation in Inflammatory Bowel Disease Pathogenesis

Cited by 290 publications

References 52 publications

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4

Osteopontin expression by CD103−dendritic cells drives intestinal inflammation

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Osteopontin expression by CD103⁻dendritic cells drives intestinal inflammation