A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress

Dixon, Christopher L.; Richardson, Lauren; Sheller‐Miller, Samantha; Saade, George R.; Menon, Ramkumar

doi:10.1111/aji.12790

Cited by 60 publications

(52 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Examination of pPROM membranes indicated signs of premature senescence activation (or accelerated aging of membranes) prior to term to oxidative stress-inducing risk factors [34,35]. In vitro, we have shown that infection, inflammation, and environmental and behavioral risk factors can accelerate cell senescence in fetal membranes [20,21,24,36]. Thus, senescence-associated cellular level changes in fetal membranes contribute to an inflammatory process by not only weakening the membranes but disabling their functional capabilities.…”

Section: Senescence Of Fetal Membranesmentioning

confidence: 85%

“…Generation of balanced inflammation maintains membrane integrity through controlled remodeling whereas persistence of inflammation either due to physiologic (term) or pathologic (preterm) can be considered as fetal/host inflammatory response causing membrane weakening, rupture [16]. The inflammation observed in fetal membranes is 'sterile inflammation' [20] during normal pregnancy that are physiologic host response whereas the contributors of inflammation in preterm membranes are often 'infectious' [21] in response to microbial invasion of the amniotic cavity. Sterile inflammation is also reported in the absence of infection in pregnancy pathologies in response to various non-infectious risk factors [20].…”

Section: Senescence Of Fetal Membranesmentioning

confidence: 99%

See 1 more Smart Citation

Fetal membrane architecture, aging and inflammation in pregnancy and parturition

2019

Self Cite

View full text Add to dashboard Cite

Preterm birth is the single major cause of infant mortality. Short and long term outcomes for infants are often worse in cases of preterm premature rupture of the fetal membranes (pPROM). Thus, increased knowledge of the structure characteristics of fetal membranes as well as the mechanisms of membrane rupture are essential if we are to develop effective treatment strategies to prevent pPROM. In this review, we focus on the role of inflammation and senescence in fetal membrane biology.

show abstract

Section: Senescence Of Fetal Membranesmentioning

confidence: 85%

Section: Senescence Of Fetal Membranesmentioning

confidence: 99%

Fetal membrane architecture, aging and inflammation in pregnancy and parturition

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the transmission electron microscopy (TEM) analysis, sEV samples were fixed in 3% (w/v) glutaraldehyde and analysed as previously described [40,41]. Briefly, 5 µL of each sample was adsorbed on Formvar carbon-coated and glow-discharged electron microscopy grids.…”

Section: Salivary Sevs Characterisationmentioning

confidence: 99%

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Han

Bartold

Salomón

et al. 2020

IJMS

View full text Add to dashboard Cite

This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

show abstract

“…Fetal membranes collected on different gestational days were lysed with RIPA lysis buffer (50 mmol/L Tris pH 8.0, 150 mmol/L NaCl, 1% Triton X‐100, and 1.0 mmol/L EDTA pH 8.0, 0.1% SDS) supplemented with protease and phosphatase inhibitor cocktail and phenylmethylsulfonyl fluoride as described previously by our laboratory . A Pierce BCA Protein Assay Kit (Thermo Scientific) was utilized to determine protein concentration of samples, and 45 µg of tissue lysate was used for loading the gels for Western blotting, which was performed as previously described by our laboratory . Briefly, samples were run on gradient (4%‐15%) SDS‐PAGE Mini‐PROTEAN TGX pre‐cast gels (Bio‐Rad) and transferred to the membrane using a Bio‐Rad gel transfer device (Bio‐Rad).…”

Section: Methodsmentioning

confidence: 99%

Changes in mediators of pro‐cell growth, senescence, and inflammation during murine gestation

Lavu

Sheller‐Miller

Kechichian

et al. 2020

American J Rep Immunol

Self Cite

View full text Add to dashboard Cite

Problem: Senescence of the fetal membranes and senescence-associated inflammation have been associated with parturition at term and pre-term in both mice and humans. Using a pregnant mouse model, we determined changes in multiple molecular signalers contributing to senescence and inflammation associated with parturition. Method of study:Fetal membranes were collected from timed-pregnant CD-1 mice on gestation days (E) 13, 15, 17, 18, and 19. Immunohistochemistry (IHC) localized pro-cell growth factors glycogen synthase kinase 3β (GSK3β) and β-catenin. Gestational age-associated changes in pro-cell growth vs senescence mediators (p38 mitogen-activated protein kinase [p38MAPK]), prooxidants (heme oxygenase-1 [HO-1], peroxisome proliferator-activated receptor γ [PPARγ]), and pro-and anti-inflammatory cytokines (IL-6, IL-8, IL-10, and IL-1β) were determined by Western blots and Luminex assays. Results: Fetal membrane expressions of phosphorylated forms of GSK3β (inactivation) and p38MAPK (activation) increased, while β-catenin expression decreased, as gestation progressed. Antioxidant HO-1 expression decreased while PPARγ increased toward term gestation. IL-6 and IL-8 concentrations were highest on E19 (day of delivery), while IL-10 and IL-1β concentrations were highest on E15. Conclusion: Mouse fetal membranes showed a progressive senescence marker increase coincided with downregulation of cell growth factors. Development of senescence is associated with inflammation. Senescence-associated changes are natural and physiologic and indicative of fetal membranes' readiness for parturition. K E Y W O R D Sfetal membranes, GSK3β, oxidative stress, p38MAPK, pre-term labor, senescence

show abstract

A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress

Abstract: TNF-α caused OS-mediated p38MAPK induction, senescence, and IL-6 increase from AECs. LPS also induced senescence and IL-6 increase. Inflammatory and infectious factors may cause premature fetal cell senescence contributing to preterm birth pathophysiology.

Cited by 60 publications

References 48 publications

Fetal membrane architecture, aging and inflammation in pregnancy and parturition

Fetal membrane architecture, aging and inflammation in pregnancy and parturition

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status—A Pilot Study

Changes in mediators of pro‐cell growth, senescence, and inflammation during murine gestation

Contact Info

Product

Resources

About