Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis

Liu, Jingquan; Shi, Bin; Shi, Kai; Ma, Guoguang; Zhang, Hongze; Lou, Xiaoli; Liu, Hongxiang; Wan, Shengxia; Dong, Liang

doi:10.1016/j.biopha.2016.12.026

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…PepT1 can also be regulated by ghrelin (an orexigenic hormone). Liu et al 39 proposed that the uptake function of PepT1 can be upregulated by ghrelin, the small intestine epithelium of rats, and the expression of PepT1 both in the protein and mRNA levels was higher in ghrelin-treated group rats. This may be a transcriptional regulation even though the molecular mechanisms are still unclear.…”

Section: Regulation By Hormonesmentioning

confidence: 99%

Regulation profile of the intestinal peptide transporter 1 (PepT1)

Wang

Liu

Xie

et al. 2017

DDDT

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The intestinal peptide transporter 1 (PepT1) was first identified in 1994. It plays a crucial role in the absorption of small peptides including not only >400 different dipeptides and 8,000 tripeptides digested from dietary proteins but also a repertoire of structurally related compounds and drugs. Owing to its critical role in the bioavailability of peptide-like drugs, such as the anti-cancer agents and anti-virus drug, PepT1 is increasingly becoming a striking prodrug-designing target. Therefore, the understanding of PepT1 gene regulation is of great importance both for dietary adaptation and for clinical drug treatment. After decades of research, it has been recognized that PepT1 could be regulated at the transcriptional and post-transcriptional levels by numerous factors. Therefore, the present review intends to summarize the progress made in the regulation of PepT1 and provide insights into the PepT1’s potential in clinical aspects of nutritional and drug therapies.

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Section: Regulation By Hormonesmentioning

confidence: 99%

Regulation profile of the intestinal peptide transporter 1 (PepT1)

Wang

Liu

Xie

et al. 2017

DDDT

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“…Sepsis is a systemic inflammatory response caused by infection and is one of the most problematic critical illnesses in critical care medicine [25, 26]. When sepsis occurs, the gastrointestinal tract is first involved, the internal environment is imbalanced, inflammatory factor products increase, apoptosis increases, and the intestinal mucosa and epithelium become necrotic, resulting in the destruction of the intestinal mucosal barrier, changes in mucosal permeability, dysbiosis of the intestinal flora and the occurrence of flora translocation, which eventually lead to the occurrence of bacteraemia and multiple organ dysfunction syndrome, causing irreversible and serious damage to the patient [27, 28]. Thus, alterations in gastrointestinal function play a crucial role in the pathogenesis of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis

Zou

Huang

et al. 2023

Digestion

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Introduction: Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis. Methods: A mouse caecal ligation and puncture method was used to construct a mouse sepsis model. Firstly, damage to intestinal tissues at different time points was analysed. The levels of Cx43, miR-181b, Sirt1, and FOXO3a in intestinal tissues and the transcription and translation of the apoptosis-related genes Bim and puma, which are downstream of FOXO3a were analysed. Secondly, the effect of Cx43 levels on miR-181b and Sirt1/FOXO3a signalling pathway activity was explored by using the Cx43 inhibitor heptanol. Finally, luciferase assays were used to determine miR-181b binding to the predicted target sequence. Results: The results show that during sepsis, intestinal injury becomes increasingly worse with time, and the expression of Cx43 and miR-181b increase. In addition, we found that heptanol could significantly reduce intestinal injury. This finding indicates that inhibiting Cx43 regulates the transfer of miR-181b between adjacent cells, thereby reducing the activity of the Sirt1/FOXO3a signalling pathway and reducing the degree of intestinal injury during sepsis. Conclusions: In sepsis, the enhancement of Cx43 gap junctions leads to an increase in miR-181b intercellular transfer, affects the downstream SIRT1/FOXO3a signalling pathway and causes cell and tissue damage.

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“…Increases the expression of PepT1. [71] Immunity ↑ Increases proliferation of CD4 T cells. [72] Apoptosis ↓ Inhibits apoptosis of gastric epithelial cells.…”

Section: Ghrelin and Gi Sepsismentioning

confidence: 99%

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Wu,

Zhu,

Dou

et al. 2024

CIMB

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This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.

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Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis

Cited by 8 publications

References 34 publications

Regulation profile of the intestinal peptide transporter 1 (PepT1)

Regulation profile of the intestinal peptide transporter 1 (PepT1)

Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

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