Numb modulates intestinal epithelial cells toward goblet cell phenotype by inhibiting the Notch signaling pathway

Abstract Background: Previous studies have suggested that Helicobacter pylori (H. pylori, Hp) infection has a protective function in inflammatory bowel disease (IBD); Exosomes (Exo) are novel cell-cell communication mediators and their association with inflammatory immune responses has received great attention. however the mechanisms regarding the role of exosomes between Hp infection and IBD are limited.Methods: Human intestinal epithelial cells were treated with serum exosomes derived from Hp-positive chronic gastritis patients (Exo(Hp)), the expression of cytokines, inflammasome and signal pathway genes were detected by antibody microarray or PCR array. Furthermore, DSS-induced colitis mice were treated with exosomes by intraperitoneally injection to study the effect of Exo(Hp) in IBD.Results: Serum exosomes derived from Hp-positive chronic gastritis patients promoted NLRP12 expression in intestinal epithelial cells, and NLRP12 decreased chemokine MCP-1 and MIP-1α expression by inhibiting the Notch signaling pathway. In vivo, Exo(Hp) could attenuated inflammatory responses in DSS-induced colitis and improved colitis symptoms, which was associated with the increase in NLRP12 expression. Furthermore, the immunohistochemistry results showed that NLRP12 was negatively correlated with the disease activity of pediatric IBD patients. Conclusions: Exo(Hp) inhibited the Notch signaling pathway through the promotion of NLRP12 expression to further down-regulate MCP-1 and MIP-1α expression in intestinal epithelial cells and thereby attenuate DSS-induced colitis in mice. These results provide new theoretical bases for further elucidation of the intestinal protection mechanisms of Hp infection in IBD, and provide new targets for explorations of effective interventional strategies for IBD.

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Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway

Marine Drugs ◽

10.3390/md17040205 ◽

2019 ◽

Vol 17 (4) ◽

pp. 205

Author(s):

Su-Jin Jeong ◽

Jeong-Wook Choi ◽

Min-Kyeong Lee ◽

Youn-Hee Choi ◽

Taek-Jeong Nam

Keyword(s):

Cell Cycle ◽

Epithelial Cells ◽

Signaling Pathway ◽

Crude Protein ◽

Cell Cycle Progression ◽

Intestinal Epithelial Cells ◽

Mapk Signaling ◽

S Phase ◽

Intestinal Epithelial ◽

Cycle Progression

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

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The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development

Blood ◽

10.1182/blood-2010-11-319129 ◽

2011 ◽

Vol 118 (7) ◽

pp. 1989-1997 ◽

Cited By ~ 61

Author(s):

Kyle Niessen ◽

Gu Zhang ◽

John Brady Ridgway ◽

Hao Chen ◽

Ganesh Kolumam ◽

...

Keyword(s):

Blood Vessel ◽

Notch Signaling ◽

Signaling Pathway ◽

Lymphatic Vessels ◽

Mouse Skin ◽

Notch Signaling Pathway ◽

Cell Phenotype ◽

Mural Cell ◽

Lymphatic Development ◽

Vessel Development

Abstract The Notch signaling pathway plays a fundamental role during blood vessel development. Notch signaling regulates blood vessel morphogenesis by promoting arterial endothelial differentiation and pro-viding spatial and temporal control over “tip cell” phenotype during angiogenic sprouting. Components of the Notch signaling pathway have emerged as potential regulators of lymphatic development, joining the increasing examples of blood vessel regulators that are also involved in lymphatic development. However, in mammals a role for the Notch signaling pathway during lymphatic development remains to be demonstrated. In this report, we show that blockade of Notch1 and Dll4, with specific function-blocking antibodies, results in defective postnatal lymphatic development in mice. Mechanistically, Notch1-Dll4 blockade is associated with down-regulation of EphrinB2 expression, been shown to be critically involved in VEGFR3/VEGFC signaling, resulting in reduced lymphangiogenic sprouting. In addition, Notch1-Dll4 blockade leads to compromised expression of distinct lymphatic markers and to dilation of collecting lymphatic vessels with reduced and disorganized mural cell coverage. Finally, Dll4-blockade impairs wound closure and severely affects lymphangiogenesis during the wound healing in adult mouse skin. Thus, our study demonstrates for the first time in a mammalian system that Notch1-Dll4 signaling pathway regulates postnatal lymphatic development and pathologic lymphangiogenesis.

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869 Up-Regulation of Delta1 Expression is Required for Goblet Cell Differentiation in Human Intestinal Epithelial Cells

Gastroenterology ◽

10.1016/s0016-5085(10)60553-7 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-120-S-121

Author(s):

Junko Akiyama ◽

Ryuichi Okamoto ◽

Kiichiro Tsuchiya ◽

Tetsuya Nakamura ◽

Mamoru Watanabe

Keyword(s):

Cell Differentiation ◽

Epithelial Cells ◽

Goblet Cell ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Human Intestinal Epithelial Cells ◽

Goblet Cell Differentiation

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Tu1402 All-Trans Retinoic Acid (ATRA) Stimulates SLC26A3 Activity in Intestinal Epithelial Cells via a PI3K Signaling Pathway

Gastroenterology ◽

10.1016/s0016-5085(15)32989-9 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-880 ◽

Cited By ~ 1

Author(s):

Shubha Priyamvada ◽

Arivarasu Natarajan Anbazhagan ◽

Anoop Kumar ◽

Tarunmeet Gujral ◽

Alip Borthakur ◽

...

Keyword(s):

Retinoic Acid ◽

Epithelial Cells ◽

Signaling Pathway ◽

Intestinal Epithelial Cells ◽

Pi3k Signaling ◽

Intestinal Epithelial ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Pi3k Signaling Pathway

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Treatment of Intrauterine Adhesions with Human Amnion Mesenchymal Stromal Cells (hAMSCs) on Promoting Endometrial Regeneration and Repair Via Notch Signaling Pathway Regulation

10.21203/rs.3.rs-92874/v1 ◽

2020 ◽

Author(s):

Jie Yu ◽

Wenwen Zhang ◽

Jiayue Huang ◽

Yating Gou ◽

Congcong Sun ◽

...

Keyword(s):

Epithelial Cells ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Intrauterine Adhesions ◽

Epithelial Markers ◽

Qrt Pcr ◽

Endometrial Epithelial Cells

Abstract Background: Human amniotic mesenchymal stem cells(hAMSCs) can repair and improve the damaged endometrium which its aplastic disorder is the main reason for intrauterine adhesions(IUAs).Methods: We conducted in vivo and in vitro experiments. In vivo experiments: 45 female Sprague-Dawley(SD) rats were involved and randomized equally into Sham group, IUA group, Estradiol(E2) group, hAMSCs group, and E2 + hAMSCs group. The effect of hAMSCs and E2 only or combined was evaluated by Hematoxylin-eosin(HE) and Masson staining. The expression of epithelial markers and key proteins of Notch signaling pathway by Immunohistochemistry. In vitro experiments: Firstly, the hAMSCs cells were taken and divided into control group and induced group in which hAMSCs were differentiated into endometrial epithelial cells in induced microenvironment, and extracted their RNA respectively. The expression of epithelial markers and Notch1 messenger RNA (mRNA) was detected by Real-time quantitative polymerase chain reaction(qRT-PCR). and the changes in expression position of Notch intracellular domain(NICD) and expression amount of target gene, hairy enhancer of split 1(Hes1) were detected by Immunofluorescence. Then, Activated and inhibited the Notch signaling pathway while induction, and detected mRNA expression of hAMSCs epithelial markers by quantitative real-time polymerase chainreaction (qRT-PCR) respectively and detected hAMSCs cell cycle by flow cytometric. Results:This study showed that hAMSCs alone or combined with E2 could promote endometrial repair, and Notch signaling pathway a great role in it. And otherwise, the activation or habitation of Notch signaling pathway determines whether hAMSCs could differentiate into endometrial epithelial cells or not.Conclusion: we concluded that activate the Notch signaling pathway promote the differentiation of hAMSCs into endometrial epithelial cells, and further treat IUAs.

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