scholarly journals IL-33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization

2018 ◽  
Author(s):  
Zhengxiang He ◽  
Lili Chen ◽  
Glaucia C. Furtado ◽  
Sergio A. Lira
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Full Length ◽  
Nuclear Accumulation ◽  
List Type ◽  
Intestinal Epithelial ◽  
Regulated Gene Expression

AbstractIL-33 is a cytokine found in the extracellular space (mature IL-33) or in the cell nucleus (full-length IL-33). Nuclear accumulation of IL-33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL-33inIEC, we generated transgenic mice expressing full-length IL-33inthe intestinal epithelium (Vfl33mice). Expression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33. Over-expression of full-length IL-33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL-33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL-33,weintercrossed theVfl33mice with ST2-deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL-33 expression, suggesting that the transcriptional effects of IL-33 on IEC are mediated by its mature, not its nuclear form.HighlightsExpression of full-length IL-33 in the epithelium resulted in accumulation of IL-33 protein in the nucleus and secretion of IL-33.Full-length IL-33 induced differential gene expression in IEC and LPL that was negatively associated with intestinal inflammatory diseasesIL-33 regulated gene expression in IEC via its extracellular (mature) form not via its nuclearform.

scholarly journals Activation of Wnt3a signaling stimulates intestinal epithelial repair by promoting c-Myc-regulated gene expression

2012 ◽  
Vol 302 (1) ◽  
pp. C277-C285 ◽  
Author(s):  
Lan Liu ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Xiao ◽  
Alexis Smith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cyclin E ◽  
Cell Renewal ◽  
Intestinal Epithelial ◽  
Epithelial Repair ◽  
Myc Gene ◽  
Factor C ◽  
Regulated Gene Expression

In response to mucosal injury, epithelial cells modify the patterns of expressed genes to repair damaged tissue rapidly. Our previous studies have demonstrated that the transcription factor c-Myc is necessary for stimulation of epithelial cell renewal during mucosal healing, but the up-stream signaling initiating c-Myc gene expression after injury remains unknown. Wnts are cysteine-rich glycoproteins that act as short-range ligands to locally activate receptor-mediated signaling pathways and correlate with the increased expression of the c-Myc gene. The current study tested the hypothesis that Wnt3a signaling is implicated in intestinal epithelial repair after wounding by stimulating c-Myc expression. Elevated Wnt3a signaling in intestinal epithelial cells (IEC-6 line) by coculturing with stable Wnt3a-transfected fibroblasts or ectopic overexpression of the Wnt3a gene enhanced intestinal epithelial repair after wounding. This stimulatory effect on epithelial repair was prevented by silencing the Wnt coreceptor LRP6 or by c-Myc silencing. Activation of the Wnt3a signaling pathway increased β-catenin nuclear translocation by decreasing its phosphorylation and stimulated c-Myc expression during epithelial repair after wounding. In stable Wnt3a-transfected IEC-6 cells, increased levels of c-Myc were associated with an increase in expression of c-Myc-regulated genes cyclcin D1 and cyclin E, whereas c-Myc silencing inhibited expression of cyclin D1 and cyclin E and delayed epithelial repair. These results indicate that elevated Wnt3a signaling in intestinal epithelial cells after wounding stimulates epithelial repair by promoting c-Myc-regulated gene expression.

scholarly journals Temporal induction of intestinal epithelial hypoxia-inducible factor-2α is sufficient to drive colitis

2019 ◽  
Vol 317 (2) ◽  
pp. G98-G107 ◽  
Author(s):  
Sumeet Solanki ◽  
Samantha N. Devenport ◽  
Sadeesh K. Ramakrishnan ◽  
Yatrik M. Shah
Keyword(s):  
Inflammatory Bowel Disease ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Hypoxia Inducible Factor ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

Hypoxia is a notable feature of inflammatory bowel disease and chronic induction of hypoxia-inducible factor (HIF)-1α and HIF-2α (endothelial PAS domain protein 1, EPAS1) play important, but opposing, roles in its pathogenesis. While activation of HIF-1α decreases intestinal inflammation and is beneficial in colitis, activation of HIF-2α exacerbates colitis and increases colon carcinogenesis in animal models, primarily due to the role of epithelial HIF-2α in mounting a potent inflammatory response. Previous work from our laboratory showed that mice overexpressing intestinal epithelial HIF-2α led to massive intestinal inflammation and decreased survival. As oxygen homeostasis and HIFs are critical in embryonic development, it is not clear whether the observed intestinal inflammatory response was secondary to developmental defects. To address this question, the present study used a mouse model to temporally modulate expression of intestinal epithelial HIF-2α to assess its role in mediating inflammatory response. Remarkably, activation of HIF-2α in intestinal epithelial cells in adult mice increased expression of proinflammatory mediators; however, no decrease in survival was observed. Furthermore, in an acute model of colitis, activation of HIF-2α was sufficient to exacerbate colitis. These data confirm our previous finding that epithelial HIF-2α mediates inflammatory response and demonstrates that activation of HIF-2α is sufficient to exacerbate colitis.NEW & NOTEWORTHY Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestinal tract. Hypoxia and activation of its downstream transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α are notable features of IBD. HIF-1α has well-characterized protective roles in IBD; however, the role of HIF-2α has been less studied. Using novel HIF-2α mouse models, we show that activation of HIF-2α in intestinal epithelial cells is sufficient to exacerbate colitis.

Tu1757 - The Role of Autophagy in Intestinal Epithelial Cells in Intestinal Inflammation

2018 ◽  
Vol 154 (6) ◽  
pp. S-1011
Author(s):  
Kazuki Kakimoto ◽  
Minori Kubota ◽  
Kei Nakazawa ◽  
Yuki Hirata ◽  
Taisuke Sakanaka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

scholarly journals Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial Inflammation through Inhibiting NF-κB Pathway and TNF-α

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Zhang ◽  
Zhongqiu Wang ◽  
Jun Liu ◽  
Zhenyu Zhang ◽  
Ye Chen
Keyword(s):  
Epithelial Cells ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Intestinal Epithelial Cells ◽  
Underlying Mechanism ◽  
Intestinal Epithelial ◽  
Cell Models ◽  
Tnf Α ◽  
Epithelial Inflammation

Syndecan-1 (SDC1), with a long variable ectodomain carrying heparan sulfate chains, participates in many steps of inflammatory responses. But reports about the efforts of SDC1’s unshedding ectodomain on intestinal epithelial inflammation and the precise underlying mechanism are limited. In our study, unshedding SDC1 from intestinal epithelial cell models was established by transfecting with unshedding SDC1 plasmid into the cell, respectively. And the role of unshedding SDC1 in intestinal inflammation was further investigated. We found that components of NF-κB pathway, including P65 and IκBα, and secretion of TNF-αwere upregulated upon LPS stimulation in intestinal epithelial cells. SDC1, especially through its unshed ectodomain, significantly lessened the upregulation extent. It also functioned in inhibiting migration of neutrophils by downregulating secretion of CXCL-1. Taken together, we conclude that suppressing SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation by inactivating NF-κB pathway and downregulating TNF-αexpression. These results indicate that the ectodomain of SDC1 might be the optional therapy for intestinal inflammation.

Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Fungal Protein ◽  
Fungal Immunomodulatory Protein

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...

scholarly journals CDX2 regulates interleukin‐33 gene expression in intestinal epithelial cells (LS174T)

FEBS Open Bio ◽  
2021 ◽  
Author(s):  
Sylvester Larsen ◽  
Jakob Benedict Seidelin ◽  
Johanne Davidsen ◽  
Katja Dahlgaard ◽  
Claus Henrik Nielsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Interleukin 33

scholarly journals Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ti-Dong Shan ◽  
Han Yue ◽  
Xue-Guo Sun ◽  
Yue-Ping Jiang ◽  
Li Chen
Keyword(s):  
Epithelial Cells ◽  
Bioinformatics Analysis ◽  
Intestinal Epithelial Cells ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Diabetic State ◽  
Definitive Evidence

Abstract Background The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism. Methods Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM. Results Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression. Conclusions Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.

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