scholarly journals Inhibition of HtrA2 alleviated colitis by preventing necroptosis of intestinal epithelial cells

2018 ◽  
Author(s):  
Chong Zhang ◽  
Andong He ◽  
Shuai Liu ◽  
Qiaoling He ◽  
Yiqin Luo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rational Design ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Tandem Mass Tag ◽  
Function Loss

AbstractNecroptosis of intestinal epithelial cells has been indicated to play an important role in the pathogenesis of inflammatory bowel disease (IBD). The identification of dysregulated proteins that can regulate necroptosis in dextran sulfate sodium (DSS)-induced colitis is the key to the rational design of therapeutic strategies for colitis. Through Tandem Mass Tag (TMT)-based quantitative proteomics, HtrA2 was found to be downregulated in the colon of DSS-treated mice. UCF-101, a specific serine protease inhibitor of HtrA2, significantly alleviated DSS-induced colitis as indicated by prevention of body weight loss and decreased mortality. UCF-101 decreased DSS-induced colonic inflammation, prevented intestinal barrier function loss and inhibited necroptosis of intestinal epithelial cells. In vitro, UCF-101 or silencing of HtrA2 decreased necroptosis of HT-29 and L929 cells. UCF-101 decreased phosphorylation of RIPK1 and subsequent phosphorylation of RIPK3 and MLKL during necroptosis. HtrA2 directly interacted with RIPK1 and promoted its degradation during a specific time phase of necroptosis. Our findings highlight the importance of HtrA2 in regulating colitis by modulation of necroptosis and suggest HtrA2 as an attractive target for anti-colitis treatment.

scholarly journals PTPN2 Regulates Interactions Between Macrophages and Intestinal Epithelial Cells to Promote Intestinal Barrier Function

2020 ◽  
Vol 159 (5) ◽  
pp. 1763-1777.e14 ◽  
Author(s):  
Marianne R. Spalinger ◽  
Anica Sayoc-Becerra ◽  
Alina N. Santos ◽  
Ali Shawki ◽  
Vinicius Canale ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

Potassium Channels in Intestinal Epithelial Cells and their Pharmacological Modulation: A Systematic Review

2020 ◽  
Author(s):  
Dina Cosme ◽  
Maria Manuela Estevinho ◽  
Florian Rieder ◽  
Fernando Magro
Keyword(s):  
Epithelial Cells ◽  
Potassium Channels ◽  
Intestinal Epithelial Cells ◽  
Strong Association ◽  
Physiological Role ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Pharmacological Modulation ◽  
Inflammatory Bowel

Background: Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characteristics and modulation of KCs in intestinal epithelial cells (IECs). Methods: PubMed, Scopus and Web of Science were searched to identify studies focusing on KCs and their modulation in IECs. The included studies were assessed using a reporting inclusiveness checklist. Results: From the 745 identified records, 73 met the inclusion criteria; their reporting inclusiveness was moderate-high. Some studies described the physiological role of KCs, while others explored their importance in pathological settings. Globally, in IBD animal models, apical KCa1.1 channels, responsible for luminal secretion, were upregulated. In human colonocytes, basolateral KCa3.1 channels were downregulated. The pharmacological inhibition of K2P and Kv influenced intestinal barrier function, promoting inflammation. Conclusion: Evidence suggests a strong association between KCs expression and secretory mechanisms in human and animal IECs. Further research is warranted to explore the usefulness of KC pharmacological modulation as a therapeutic target.

scholarly journals A novel two-compartment barrier model for investigating nanoparticle transport in fish intestinal epithelial cells

2016 ◽  
Vol 3 (2) ◽  
pp. 388-395 ◽  
Author(s):  
Mark Geppert ◽  
Laura Sigg ◽  
Kristin Schirmer
Keyword(s):  
Rainbow Trout ◽  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Nanoparticle Transport ◽  
Barrier Model

We introduce a novel in vitro rainbow trout intestinal barrier model and demonstrate its suitability for investigating nanoparticle transport across the intestinal epithelium.

scholarly journals 124 Butyric acid and derivatives: In vitro effects on barrier integrity of porcine intestinal epithelial cells quantified by transepithelial electrical resistance

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 109-110
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Butyric Acid ◽  
Sodium Butyrate ◽  
Barrier Function ◽  
Electrical Resistance ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Transepithelial Electrical Resistance ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial

Abstract Intestinal barrier function in vitro is quantified by the transepithelial electrical resistance (TEER) across epithelial cell monolayers due to polarization and expression of tight junction proteins. The objective of the current study was to measure the TEER of porcine intestinal epithelial cells (IPEC-J2) treated with butyric acid, sodium butyrate, monobutyrin and tributyrin. MTT assays were performed for each compound to determine cell viability and appropriate treatment doses. Butyric acid and tributyrin treatments were: 0, 0.5, 1, 2, and 4 mM. Monobutyrin and sodium butyrate doses were: 0, 1, 2, 4, 8 mM. Cells were seeded at 5 × 105 cells/mL into 12-well plates on Corning transwell inserts. Cells were cultured for 4 to 5 days (until all wells had TEER close to 1000 Ωcm2) and were then treated with organic acids. Each compound was tested in a randomized complete block design with 10 replicates. TEER was measured in Ωcm2 using a Millicell ERS-2 voltohmmeter at 0 h (before treatment) and at 24, 48, and 72 h post-treatment. All data were analyzed by PROC MIXED of SAS. Butyric acid linearly enhanced (P < 0.001) TEER of IPEC-J2 dose-dependently, with the highest TEER observed at doses of 1 and 2 mM at each time point. Sodium butyrate did not impact TEER at h 24, but linearly increased (P < 0.05) TEER at h 48 and 72. Treatment of monobutyrin linearly improved (P < 0.001) TEER at h 24, 48, and 72, with the highest TEER observed at the dose of 8 mM. Tributyrin had the tendency to improve (P < 0.10) TEER at h 48 and 72 when the highest dose was applied. Results of the current in vitro study indicate that butyric acid and its derivatives may improve intestinal barrier function of pigs, which requires verification in vivo.

scholarly journals Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danyang Zheng ◽  
Henan Zhou ◽  
Hongchen Wang ◽  
Yu Zhu ◽  
Yue Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Dynamic Balance ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Mitochondrial Dynamic ◽  
Intestinal Barrier Dysfunction

Abstract Background Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure. Methods In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated. Results MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly. Conclusion MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.

scholarly journals In vitro effect of uremic serum on barrier function and inflammation in human colonocytes

2018 ◽  
Vol 40 (3) ◽  
pp. 217-224 ◽  
Author(s):  
Laila Santos de Andrade ◽  
Maria Aparecida Dalboni ◽  
José Tarcisio Giffoni de Carvalho ◽  
Caren Cristina Grabulosa ◽  
Natalia Barros Ferreira Pereira ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Potential Effect ◽  
Intestinal Epithelial ◽  
T84 Cells ◽  
Uremic Serum ◽  
Inflammatory State ◽  
Vitro Effect

ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

scholarly journals Clostridioides difficile spore-entry into intestinal epithelial cells contributes to recurrence of the disease

2020 ◽  
Author(s):  
Pablo Castro-Córdova ◽  
Paola Mora-Uribe ◽  
Rodrigo Reyes-Ramírez ◽  
Glenda Cofré-Araneda ◽  
Josué Orozco-Aguilar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Mucosa ◽  
Rational Design ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Recurrent Infection ◽  
Intestinal Epithelial ◽  
Clostridioides Difficile ◽  
Infection Recurrence

AbstractClostridioides difficile spores produced during infection are essential for the recurrence of the disease. However, how C. difficile spores persist in the intestinal mucosa to cause recurrent infection remains unknown. Here, we show that C. difficile spores gain entry into the intestinal mucosa via fibronectin-α5β1 and vitronectin-αvβ1 specific-pathways. The spore-surface exosporium BclA3 protein is essential for both spore-entry pathways into intestinal epithelial cells. Furthermore, C. difficile spores of a bclA3 isogenic mutant exhibited reduced entry into the intestinal mucosa and reduced recurrence of the disease in a mouse model of the disease. Inhibition of C. difficile spore-entry led to reduced spore-entry into the intestinal epithelial barrier and recurrence of C. difficile infection in vivo. These findings suggest that C. difficile spore-entry into the intestinal barrier is a novel mechanism of spore-persistence that can contribute to infection recurrence and have implications for the rational design of therapies.

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