EGF suppresses intestinal epithelial cell shedding both in vitro and in vivo via a MEK/ERK dependent pathway

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Mark R Frey ◽  
Jennifer C Miguel ◽  
Ching‐Ling Lien ◽  
Alastair J Watson
Keyword(s):  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Cell Shedding ◽  
Dependent Pathway

Effects of lactoferrin on intestinal epithelial cell growth and differentiation: an in vivo and in vitro study

BioMetals ◽  
2014 ◽  
Vol 27 (5) ◽  
pp. 857-874 ◽  
Author(s):  
Anne Blais ◽  
Cuibai Fan ◽  
Thierry Voisin ◽  
Najat Aattouri ◽  
Michel Dubarry ◽  
...  
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
In Vitro Study ◽  
Vitro Study ◽  
Intestinal Epithelial ◽  
Cell Growth And Differentiation

scholarly journals Deficiency in the anti-apoptotic protein DJ-1 promotes intestinal epithelial cell apoptosis and aggravates inflammatory bowel disease via p53

2020 ◽  
Vol 295 (13) ◽  
pp. 4237-4251 ◽  
Author(s):  
Jie Zhang ◽  
Min Xu ◽  
Weihua Zhou ◽  
Dejian Li ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cell ◽  
Bowel Disease ◽  
Intestinal Epithelial Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial ◽  
P53 Expression ◽  
Inflammatory Bowel

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1−/− mice, DJ-1−/−p53−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.

The influence of protein fractions from bovine colostrum digested in vivo and in vitro on human intestinal epithelial cell proliferation

2014 ◽  
Vol 81 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Alison J Morgan ◽  
Lisa G Riley ◽  
Paul A Sheehy ◽  
Peter C Wynn
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Proliferative Activity ◽  
Intestinal Epithelial Cell ◽  
Bovine Colostrum ◽  
Intestinal Epithelial ◽  
Epithelial Cell Proliferation ◽  
Human Intestinal Epithelial Cell

Colostrum consists of a number of biologically active proteins and peptides that influence physiological function and development of a neonate. The present study investigated the biological activity of peptides released from first day bovine colostrum through in vitro and in vivo enzymatic digestion. This was assessed for proliferative activity using a human intestinal epithelial cell line, T84. Digestion of the protein fraction of bovine colostrum in vitro was conducted with the enzymes pepsin, chymosin and trypsin. Pepsin and chymosin digests yielded protein fractions with proliferative activity similar to that observed with undigested colostrum and the positive control foetal calf serum (FCS). In contrast trypsin digestion significantly (P<0·05) decreased colostral proliferative activity when co-cultured with cells when compared with undigested colostrum. The proliferative activity of undigested colostrum protein and abomasal whey protein digesta significantly increased (P<0·05) epithelial cell proliferation in comparison to a synthetic peptide mix. Bovine colostrum protein digested in vivo was collected from different regions of the gastrointestinal tract (GIT) in newborn calves fed either once (n=3 calves) or three times at 12-h intervals (n=3 calves). Digesta collected from the distal duodenum, jejunum and colon of calves fed once, significantly (P<0·05) stimulated cell proliferation in comparison with comparable samples collected from calves fed multiple times. These peptide enriched fractions are likely to yield candidate peptides with potential application for gastrointestinal repair in mammalian species.

scholarly journals Rapid protein kinase D1 signaling promotes migration of intestinal epithelial cells

2012 ◽  
Vol 303 (3) ◽  
pp. G356-G366 ◽  
Author(s):  
Steven H. Young ◽  
Nora Rozengurt ◽  
James Sinnett-Smith ◽  
Enrique Rozengurt
Keyword(s):  
Protein Kinase ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Transgenic Mice ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Protein Kinase D1

We have examined the role of protein kinase D1 (PKD1) signaling in intestinal epithelial cell migration. Wounding monolayer cultures of intestinal epithelial cell line IEC-18 or IEC-6 induced rapid PKD1 activation in the cells immediately adjacent to the wound edge, as judged by immunofluorescence microscopy with an antibody that detects the phosphorylated state of PKD1 at Ser916, an autophosphorylation site. An increase in PKD1 phosphorylation at Ser916 was evident as early as 45 s after wounding, reached a maximum after 3 min, and persisted for ≥15 min. PKD1 autophosphorylation at Ser916 was prevented by the PKD family inhibitors kb NB 142-70 and CRT0066101. A kb NB 142-70-sensitive increase in PKD autophosphorylation was also elicited by wounding IEC-6 cells. Using in vitro kinase assays after PKD1 immunoprecipitation, we corroborated that wounding IEC-18 cells induced rapid PKD1 catalytic activation. Further results indicate that PKD1 signaling is required to promote migration of intestinal epithelial cells into the denuded area of the wound. Specifically, treatment with kb NB 142-70 or small interfering RNAs targeting PKD1 markedly reduced wound-induced migration in IEC-18 cells. To test whether PKD1 promotes migration of intestinal epithelial cells in vivo, we used transgenic mice that express elevated PKD1 protein in the small intestinal epithelium. Enterocyte migration was markedly increased in the PKD1 transgenic mice. These results demonstrate that PKD1 activation is one of the early events initiated by wounding a monolayer of intestinal epithelial cells and indicate that PKD1 signaling promotes the migration of these cells in vitro and in vivo.

14 COLONIC EPITHELIAL CELL-SPECIFIC AFTIPHILIN KNOCKDOWN REGULATES EPITHELIAL BARRIER FUNCTION THROUGH MYOSIN LIGHT CHAIN-ASSOCIATED ACTIN ORGANIZATION IN VITRO AND INTESTINAL LENGTH IN VIVO

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S28-S28
Author(s):  
Ivy Ka Man Law ◽  
Carl Rankin ◽  
Charalabos Pothoulakis
Keyword(s):  
Epithelial Cell ◽  
Barrier Function ◽  
Intestinal Epithelial Cell ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Knock Out ◽  
Epithelial Barrier Function ◽  
Actin Organization

Abstract Background and Aims Colonic epithelial integrity is often compromised during colonic inflammation and Inflammatory Bowel Disease. Aftiphilin (AFTPH) is a downstream target of microRNA-133a and its expression is reduced in colonic tissues of wild type mice from experimental colitis models and colonic biopsies from patients with ulcerative colitis. We have previously shown that AFTPH is involved in regulating intestinal epithelial barrier function and actin organization in human colonic epithelial cells in vitro (DDW 2016). On the other hand, our results suggested that global aftiphilin knock-out is embryonic lethal in mouse models (DDW 2019). Here, we further examined the role of AFTPH in regulating actin organization in vitro and characterize the colonic epithelial cell-specific aftiphilin knock-out mice. Methods Human colonic epithelial NCM460 cells were transfected with si-RNA against AFTPH to achieve transient AFTPH gene-silencing. Stable AFTPH knock-down clones were generated by transducing Caco2-BBE cells with recombinant lentivirus carrying sh-AFTPH or control sh-RNA. To create intestinal epithelial cell-specific aftiphilin knock-out mice, Aftph flox/flox mice were cross-bred with B6.Cg-Tg(Vil1-cre)997Gum/J mice, which express Villin-driven Cre recombinase (Vil-Cre), to generate intestinal epithelial cell-specific aftiphilin knock-out mice (Aftph Vil-/Vil-). Protein expression of F- and G-actin and p70S6K were detected using Western blot. Tissues from various organs were collected with Aftph Vil-/Vil- and its wildtype counterparts at 12 weeks. Results Results from western blot analysis showed that F-/G-actin ratio in AFTPH gene-silenced NCM460 cells were 0.6±0.17 fold, when compared to the treatment control. In addition, AFTPH gene-silencing in human colonic epithelial cells activated p70S6K, a kinase that is involved in actin organization, when compared to treatment control (1.2±0.15 vs. 2.0±0.15, p=0.0354). Furthermore, transepithelial electric resistance (TER) of Caco2-BBE cells deficient in AFTPH is significantly lower than that of control cells (0.5±0.07 fold). Lastly, in vivo intestinal epithelial cell-specific Aftph knock-out increased the length of small intestine, when compared to that of wild type mice (30.7±0.33 vs. 34.8±0.97, p=0.02), while the tissue weight of spleen to body weight was reduced (0.30±0.011 vs. 0.26±0.006, p=0.0169). Summary and Conclusions Our results indicate that AFTPH directly regulates epithelial barrier function and actin organization through mediating F-/G-actin ratio in human colonic epithelial cells, possibly through p70S6K. Importantly, intestinal epithelial cell-specific knock-out in vivo increased intestinal length and reduced size of the spleen. Our results suggested that AFTPH is crucial in regulating colonic epithelial barrier function in vitro and intestinal homeostasis.

scholarly journals Epidermal growth factor suppresses intestinal epithelial cell shedding through a MAPK-dependent pathway

2016 ◽  
Vol 130 (1) ◽  
pp. 90-96 ◽  
Author(s):  
Jennifer C. Miguel ◽  
Adrienne A. Maxwell ◽  
Jonathan J. Hsieh ◽  
Lukas C. Harnisch ◽  
Denise Al Alam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Epidermal Growth ◽  
Cell Shedding ◽  
Dependent Pathway

scholarly journals Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial

2020 ◽  
Vol 10 ◽  
Author(s):  
Wenhao Su ◽  
Yongyu Chen ◽  
Pan Cao ◽  
Yan Chen ◽  
Yuanmei Guo ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cell Death ◽  
Epithelial Cell ◽  
Clinical Characteristics ◽  
Intestinal Epithelial Cell ◽  
Fusobacterium Nucleatum ◽  
Autophagic Cell Death ◽  
Intestinal Epithelial

There is a growing body of evidence which suggests that intestinal microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal epithelial cell (IEC) death remained undefined. Here, we investigated the potential mechanisms about how F. nucleatum aggravates IEC death in UC. We first detected the abundance of F. nucleatum in UC tissues and analyzed its relationship with the clinical characteristics of UC. Next, we explored whether F. nucleatum promotes intestinal epithelial cell death in vitro and in vivo. Furthermore, we extracted lipopolysaccharide (LPS) of the F. nucleatum and examined whether F. nucleatum exacerbates UC via LPS. Our results indicated that F. nucleatum was abundant in UC tissues and was correlated with clinical characteristics. In addition, we demonstrated that F. nucleatum and its LPS aggravated IEC death by promoted IEC autophagy. Furthermore, autophagy inhibitors, chloroquine (CQ), 3-methyladenine (3-MA) or Atg5 silencing prevented IEC death mediated by F. nucleatum, which suggests F. nucleatum may contribute to UC by activating autophagic cell death. All our results uncover a vital role of F. nucleatum in autophagic cell death and UC, giving rise to a new sight for UC therapy by inhibiting excessive IEC autophagy and autophagic cell death.

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