Lipopolysaccharide exposure modulates the contractile and migratory phenotypes of vascular smooth muscle cells

Strela, Felipe Bichi; Brun, Bruna Ferro; Berger, Rebeca Caldeira Machado; Melo, Stéphano Freitas Soares; Oliveira, Edilamar Menezes de; Baraúna, Valério Garrone; Vassallo, Paula Frizera

doi:10.1016/j.lfs.2019.117098

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…Vimentin is a type of intermediate filament protein that is up-regulated during epithelial-to-mesenchymal transition, a process that occurs during neural development, wound healing, and cancer metastasis (34). Recently, it has been associated with sepsis (35), and therefore, this could explain high concentrations of vimentin found in saliva in a pyometra group. Haptoglobin is considered a moderate acute-phase protein in dogs, increasing its concentrations ∼2to 5-fold in serum under inflammation (36).…”

Section: Discussionmentioning

confidence: 99%

Changes in the Salivary Proteome Associated With Canine Pyometra

et al. 2020

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The present study evaluated for the first time changes in the saliva proteome in bitches with pyometra through a high-throughput quantitative proteomic analysis. The aims were to explore whether saliva composition could reflect the physiopathological changes occurring in canine pyometra and to identify potential biomarkers of the disease. Saliva samples from six healthy (H) and six bitches with pyometra (P) were analyzed using tandem mass tags-based approach. Additionally, 15 samples were used for the validation of changes in haptoglobin (Hp) concentration in saliva of dogs with pyometra. Proteomic analysis quantified 707 proteins in saliva. Comparison of the two groups revealed 16 unique proteins significantly modulated in saliva, with S100A calcium-binding protein 12 (S100A12), vimentin, and Hp the most up-regulated in canine pyometra. According to PANTHER (Protein Analysis Through Evolutionary Relationships) classification tool, these proteins are mainly related to proinflammatory mediators, acute-phase proteins, and sepsis. In conclusion, it can be stated that there are changes in various proteins in saliva in canine pyometra reflecting different physiopathological changes occurring in this disease. These proteins could be a source of potential non-invasive biomarkers for this disease that should be confirmed in future studies.

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Section: Discussionmentioning

confidence: 99%

Changes in the Salivary Proteome Associated With Canine Pyometra

et al. 2020

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“…In sepsis, alterations in the normal autoregulation of perfusion and the toxic effects of the media can lead to severe organ dysfunction [7]. Although VSMCs have been shown to play a key role in sepsis [19,20], the effect of extracellular histones on VSMCs in sepsis is unclear. In this study, we found that extracellular histones induced the senescence and in ammatory response of VSMCs in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating histones can cause cerebrovascular damage or brain dysfunction by altering the blood-brain barrier [18]. Although VSMCs play a key role in sepsis [19,20], the effect of extracellular histones on VSMCs in organ injury remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Extracellular histones induce inflammation and senescence of vascular smooth muscle cells by activating the AMPK/FOXO4 signaling pathway

et al. 2022

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Sepsis is an abnormal immune-in ammatory response that is mainly caused by infection. It can lead to life-threatening organ dysfunction and death. Severely damaged tissue cells will release intracellular histones into the circulation as damage-related molecular patterns (DAMPs) to accelerate the systemic immune response. Although various histone-related cytotoxicity mechanisms have been explored, those that affect extracellular histones involved in vascular smooth muscle cell (VSMC) dysfunction are yet to be determined. We found that extracellular histones induced senescence and in ammatory response in a dose-dependent manner in cultured VSMCs. Histone treatment signi cantly promoted apoptosisassociated speck-like protein containing CARD (ASC) as well as NACHT, LRR and PYD domainscontaining protein 3 (NLRP3) interaction of in ammasomes in VSMCs. Forkhead box protein O4 (FOXO4), which is a downstream effector molecule of extracellular histones, was found to be involved in histone-regulated VSMC in ammatory response and senescence. Furthermore, the 5'-AMP-activated protein kinase (AMPK) signaling pathway was con rmed to mediate extracellular histone-induced FOXO4 expression, and blocking this signaling pathway with an inhibitor can suppress vascular in ammation induced by extracellular histones in vivo and in vitro. These results suggest that the AMPK/FOXO4 pathway is a potential target in treating histone-mediated organ injury.

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“…LPS stimulates TLR4 signalling, enhancing inflammatory and immune responses ( Cappelletti et al 2020 ). Notably, LPS exposure modulates the contractility of vascular smooth muscle cells by increasing IL-6 secretion ( Strela et al 2020 ). However, in addition to the increased production of inflammatory cytokines, including TNFα, IL-6 and IL-22, in response to LPS ( Gomez-Lopez et al 2010 , Wakabayashi et al 2013 , Dambaeva et al 2018 ), other pathways may be involved in LPS-induced myometrial contraction.…”

Section: Discussionmentioning

confidence: 99%

RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth

et al. 2022

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Preterm birth (PTB) is a public health issue. The WHO has recommended the use of tocolytic treatment to inhibit preterm labour and improve pregnancy outcomes. Intrauterine inflammation is associated with preterm birth. Rac1 can modulate inflammation in different experimental settings. In the current study, we explored whether Rac1 can modulate spontaneous uterine myometrium contraction in a mouse model of lipopolysaccharide (LPS)-induced intrauterine inflammation. Subsequently, we recorded uterine myometrium contraction and examined uterine Rac1 expression in a mouse model of preterm birth and case in pregnant women by western blotting analysis. We also measured progesterone levels in the blood serum from mice. Murine myometrium was obtained 12 h post LPS treatment. Human myometrium was obtained at the time of caesarean section. We found that in the LPS-treated group of mice, uterine myometrium contraction was enhanced, protein levels and activation of Rac1 were increased and serum progesterone levels were decreased. The protein levels of Rac1 were also increased in preterm birth or case in pregnant women. NSC23766, a Rac1 inhibitor, attenuated uterine myometrium contraction and diminished Rac1 activation and COX-2 expression. Furthermore, silencing of Rac1 suppressed cell contraction and COX-2 expression in vitro. In conclusion, our results suggested that Rac1 may play an important role in modulating uterine myometrium contraction. Consequently, intervening with Rac1 represents a novel strategy for the treatment of preterm birth.

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Lipopolysaccharide exposure modulates the contractile and migratory phenotypes of vascular smooth muscle cells

Cited by 12 publications

References 37 publications

Changes in the Salivary Proteome Associated With Canine Pyometra

Changes in the Salivary Proteome Associated With Canine Pyometra

Extracellular histones induce inflammation and senescence of vascular smooth muscle cells by activating the AMPK/FOXO4 signaling pathway

RAC1 is involved in uterine myometrium contraction in the inflammation-associated preterm birth

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