ArticleAnnals of translational medicine2019
The pathways and mechanisms of muramyl dipeptide transcellular transport mediated by PepT1 in enterogenous infection.
Article in Annals of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 12 citations in OpenAlex.
- Article
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- Ion channels and transporters regulate nutrient absorption in health and disease.Journal of cellular and molecular medicine · 2023Review
- Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway.Journal of translational medicine · 2021Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe transcellular transport of muramyl dipeptide (MDP) mediated by peptide transporter (PepT1) involves the translocation into intestinal epithelial cell (IEC) stage and the transport out of IEC stage. However, its mechanism has not been fully understood. This study aimed to investigate the pathways and mechanisms of MDP transcellular transport in enterogenous infection.
methodsFirstly, experimental rats were randomly divided into three groups: sham-operation (sham group), MDP perfusion (MDP group), and PepT1 competitive inhibition (MDP + Gly-Gly group). Then, the overall survival (OS) and intestinal weight were measured in MDP and MDP + Gly-Gly group. HE staining was performed to observe the pathological changes of the small intestine. The levels of IL-6, IL-1b, IL-8, IL-10, TNF-α, and nitric oxide (NO) in rat serum and small intestine were determined by ELISA. To further verify the pathways and mechanisms of MDP transcellular transport from IEC in intestinal inflammatory damage, the NFκB inhibitor, PDTC, was used to treated lamina propria macrophages in small intestinal mucosa in sham, MDP, and MDP + Gly-Gly groups. Finally, the expression of CD80/86 and the antigen presentation of dendritic cells (DCs) were measured by flow cytometry.
resultsMDP infusion was able to induce death, weight loss, and intestinal pathological injury in rats. Competitive binding of Gly-Gly to PepT1 effectively inhibited these effects induced by MDP. As well, competitive of PepT1 by Gly-Gly inhibited inflammation-related cytokines induced by MDP in rat serum and small intestine. Furthermore, we also found that MDP transported by PepT1 contributes to activation of macrophages and antigen presentation of DCs.
conclusionsPepT1-NFκB signal is pivotal for activation of intestinal inflammatory response and MDP transcellular transport.
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