Neurotensin Regulates Proliferation and Stem Cell Function in the Small Intestine in a Nutrient-Dependent Manner

Rock, Stephanie B.; Jiang, Kai; Wu, Yuanyuan; Liu, Yajuan; Li, Jing; Weiss, Heidi L.; Wang, Chi; Jia, Jianhang; Gao, Tianyan; Evers, B. Mark

doi:10.1016/j.jcmgh.2021.09.006

Cited by 16 publications

(11 citation statements)

References 83 publications

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“…Furthermore, the significant reduction of NTS expression in the defunctioned intestine may also contribute to intestinal mucosal atrophy as NTS has recently been reported to regulate intestinal epithelial proliferation and stem cell function. 71 Associated with immaturity of the epithelium in the defunctioned intestine, we found a defective mechanical and mucus barrier, as well as defective metabolic absorption in the defunctioned intestine, indicating that the defunctioned intestine has a weakened ability to defend itself against pathogens. Meanwhile, faecal diversion disrupts the continuity of the intestine, which deprives the source of nutrition for microbes in the defunctioned intestine and allows oxygen to enter the intestinal lumen, leading to a reduction in microbial abundance and disruption of microbial composition.…”

Section: Discussionmentioning

confidence: 74%

“…Therefore, the absence of mechanical stimulation may be an important cause of defunctioned intestinal mucosal atrophy, and supplemental mechanical stimulation before the reversal of faecal diversion may reverse the atrophy of the defunctioned intestinal mucosa and accelerate the recovery of patients. Furthermore, the significant reduction of NTS expression in the defunctioned intestine may also contribute to intestinal mucosal atrophy as NTS has recently been reported to regulate intestinal epithelial proliferation and stem cell function 71 …”

Section: Discussionmentioning

confidence: 99%

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Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing

Pan

et al. 2023

Clinical & Translational Med

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Background Although ileal faecal diversion is commonly used in clinical settings, complications accompany it. Elucidating the intestinal changes caused by ileal faecal diversion will help resolve postoperative complications and elucidate the pathogenic mechanisms of associated intestinal disorders, such as Crohn's disease (CD). Therefore, our study aimed to provide new insights into the effects of ileal faecal diversion on the intestine and the potential mechanisms. Methods Single‐cell RNA sequencing was performed on proximal functional and paired distal defunctioned intestinal mucosae from three patients with ileal faecal diversion. We also performed in vitro cellular and animal experiments, tissue staining and analysed public datasets to validate our findings. Results We found that the epithelium in the defunctioned intestine tended to be immature, with defective mechanical and mucous barriers. However, the innate immune barrier in the defunctioned intestine was enhanced. Focusing on the changes in goblet cells, we demonstrated that mechanical stimulation promotes the differentiation and maturation of goblet cells through the TRPA1‐ERK pathway, indicating that the absence of mechanical stimulation may be the main cause of defects in the goblet cells of the defunctioned intestine. Furthermore, we found obvious fibrosis with a pro‐fibrotic microenvironment in the defunctioned intestine and identified that monocytes may be important targets for faecal diversion to alleviate CD. Conclusions This study revealed the different transcription landscapes of various cell subsets and the potential underlying mechanisms within the defunctioned intestine, when compared to the functional intestine, based on the background of ileal faecal diversion. These findings provide novel insights for understanding the physiological and pathological roles of the faecal stream in the intestine.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing

Pan

et al. 2023

Clinical & Translational Med

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“…They also showed NTS to promote ERK1/2 signaling and drive cell cycle progression and crypt proliferation under nutrient rich conditions. On the other hand, under nutrient-depleted conditions, NTS stimulated WNT/β-cat signaling promoting ISC gene signature and enhanced ISC function [13 ▪ ].…”

Section: Enteroendocrine Cell Physiology and Functionmentioning

confidence: 99%

Enteroendocrine cell differentiation and function in the intestine

Sanchez¹,

Enriquez²,

Wells

2022

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewThe intestinal enteroendocrine cells (EECs) are specialized hormone-secreting cells that respond to both circulating and luminal cues. Collectively, EECs constitute the largest endocrine organ of the body and signal to a multitude of targets including locally to neighboring intestinal cells, enteric neurons, as well as systemically to other organs, such as the pancreas and brain. To accomplish their wide range of downstream signaling effects, EECs secrete multiple hormones; however, the mechanisms that influence EEC development in the embryo and differentiation in adults are not well defined. Recent findingsThis review highlights the recent discoveries in EEC differentiation and function while also discussing newly revealed roles of transcription factors and signaling networks involved in the allocation of EEC subtypes that were discovered using a combination of novel intestinal model systems and genetic sequencing. We also discuss the potential of these new experimental models that study the mechanisms regulating EEC function and development both to uncover novel therapeutic targets. SummarySeveral EEC hormones are being used to treat various metabolic disorders, such as type 2 diabetes and obesity. Therefore, understanding the signaling pathways and gene regulatory networks that facilitate EEC formation is paramount to the development of novel therapies.

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“…This continuous self-renewal process is mediated by intestinal stem cells, which integrate dietary signals to maintain intestinal homeostasis. Both neurotensin and GLP-2 induce mucosal growth and proliferation and promote intestinal repair after inflammatory damage ( 92 ). At the molecular level, the GLP-1 receptor and the neurotensin receptor 1, which is dominating in the periphery, are coupled to Gs and Gq/11, respectively, which are signaling pathways that are well established to act synergistically ( 93 ).…”

Section: Neurotensinmentioning

confidence: 99%

Circadian hormone secretion of enteroendocrine cells: implication on pregnancy status

Homeida

Al-Suhaimi

2023

Front. Endocrinol.

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The timing of food intake is a key cue for circadian rhythms in humans and animals. In response to food intake, gut hormones called incretin are produced by intestinal enteroendocrine cells in a circadian rhythm that stimulates insulin secretion and regulates body weight and energy expenditure. Pregnancy is associated with the expansion of β cells, the risk of gestational diabetes mellitus, and excessive weight gain. The timing of food intake is a good way to address metabolic complications during pregnancy. The current review focuses on the circadian rhythms and biological actions of enteroendocrine hormones and their associations with pregnancy status, specifically topics like food intake and gut circadian rhythms, the circadian secretion of enteroendocrine peptides, and the effects of these factors during pregnancy.

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Neurotensin Regulates Proliferation and Stem Cell Function in the Small Intestine in a Nutrient-Dependent Manner

Cited by 16 publications

References 83 publications

Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing

Dissecting the effect of ileal faecal diversion on the intestine using single‐cell sequencing

Enteroendocrine cell differentiation and function in the intestine

Circadian hormone secretion of enteroendocrine cells: implication on pregnancy status

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