Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage <i>via</i> Akt signaling

Huang, Yun; Wang, Mengmeng; Yang, Zhaohui; Ren, Yi; Zhang, Wei; Sun, Zhaorui; Nie, Shaoping

doi:10.3748/wjg.v26.i48.7619

Cited by 10 publications

(6 citation statements)

References 37 publications

(12 reference statements)

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“…This is possibly due to the presence of many inflammatory factors in LPS-RAW264.7/CM, including TNF-α, and IL-6, which might lead to the protective activation of P-ERK, the binding of TFF2-Fc to CXCR4 further activated P-ERK. To some extent, this is similar to TFF3 could up-regulate LPS-activated P-AKT in gastric epithelial cells (Huang et al 2020 ). In general, these results suggested that TFF2-Fc could promote the proliferation and migration of Caco2 cells by activating P-ERK.…”

Section: Resultsmentioning

confidence: 74%

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

et al. 2023

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The clinical drugs for ulcerative colitis mainly affect the inflammatory symposiums with limited outcomes and various side effects. Repairing the damaged intestinal mucosa is a promising and alternative strategy to treat ulcerative colitis. Trefoil factor family 2 (TFF2) could repair the intestinal mucosa, however, it has a short half-life in vivo. To improve the stability of TFF2, we have prepared a new fusion protein TFF2-Fc with much stability, investigated the therapeutic effect of TFF2-Fc on ulcerative colitis, and further illustrated the related mechanisms. We found that intrarectally administered TFF2-Fc alleviated the weight loss, the colon shortening, the disease activity index, the intestinal tissue injury, and the lymphocyte infiltration in dextran sulfate sodium (DSS)-induced colitis mice. In vitro, TFF2-Fc inhibited Caco2 cells injury and apoptosis, promoted cellular migration, and increased the expression of Occludin and ZO-1 by activating P-ERK in the presence of H 2 O 2 or inflammatory conditioned medium (LPS-RAW264.7/CM). Moreover, TFF2-Fc could reduce lipopolysaccharide (LPS)-induced production of inflammation cytokines and reactive oxygen species in RAW264.7 cells, and also inhibits the polarization of RAW264.7 cells to M1 phenotype by reducing glucose consumption and lactate production. Taken together, in this work, we have prepared a novel fusion protein TFF2-Fc, which could alleviate ulcerative colitis in vivo via promoting intestinal epithelial cells repair and inhibiting macrophage inflammation, and TFF2-Fc might serve as a promising ulcerative colitis therapeutic agent.

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Section: Resultsmentioning

confidence: 74%

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

et al. 2023

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“…There are few studies on the gastroprotective effect of TFF3. Currently, it is only known that it may be achieved by activating the PI3K/AKT signaling pathway [57].…”

Section: Loudspeakermentioning

confidence: 99%

Pathological and therapeutic roles of bioactive peptide trefoil factor 3 in diverse diseases: recent progress and perspective

Yang

Lin

et al. 2022

Cell Death Dis

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Trefoil factor 3 (TFF3) is the last small-molecule peptide found in the trefoil factor family, which is mainly secreted by intestinal goblet cells and exerts mucosal repair effect in the gastrointestinal tract. Emerging evidence indicated that the TFF3 expression profile and biological effects changed significantly in pathological states such as cancer, colitis, gastric ulcer, diabetes mellitus, non-alcoholic fatty liver disease, and nervous system disease. More importantly, mucosal protection would no longer be the only effect of TFF3, it gradually exhibits carcinogenic activity and potential regulatory effect of nervous and endocrine systems, but the inner mechanisms remain unclear. Understanding the molecular function of TFF3 in specific diseases might provide a new insight for the clinical development of novel therapeutic strategies. This review provides an up-to-date overview of the pathological effects of TFF3 in different disease and discusses the binding proteins, signaling pathways, and clinical application.

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“…This was the strategy used to examine the role of trefoil factor 2 ( Tff2; also known as spasmolytic polypeptide) in restitution, which uncovered a link between Tff2 and Ca 2+ signaling in regulating restitution after injury in the stomach [17]. Tff2 peptide activated AKT signaling (a Ca 2+ -mediated cellular signaling pathway) in a rat model of stress-induced injury [18]. Trefoil factor peptides increased the rate of migration of gastric and intestinal epithelial cells after wounding [19].…”

Section: Superficial Injury and Restitutionmentioning

confidence: 99%

Mucosal defense: gastroduodenal injury and repair mechanisms

Hagen

2021

Current Opinion in Gastroenterology

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Purpose of review The mucosal barrier serves as a primary interface between the environment and host. In daily life, superficial injury to the gastric or duodenal mucosa occurs regularly but heals rapidly by a process called ‘restitution’. Persistent injury to the gastroduodenal mucosa also occurs but initiates a regenerative lesion with specific wound healing mechanisms that attempt to repair barrier function. If not healed, these lesions can be the site of neoplasia development in a chronic inflammatory setting. This review summarizes the past year of advances in understanding mucosal repair in the gastroduodenal mucosa, which occurs as a defense mechanism against injury. Recent findings Organoids are an emerging new tool that allows for the correlation of in vivo and in vitro models; organoids represent an important reductionist model to probe specific aspects of injury and repair mechanisms that are limited to epithelial cells. Additionally, proof-of-concept studies show that machine learning algorithms may ultimately assist with identifying novel, targetable pathways to pursue in therapeutic interventions. Gut-on-chip technology and single cell RNA-sequencing contributed to new understanding of gastroduodenal regenerative lesions after injury by identifying networks and interactions that are involved in the repair process. Summary Recent updates provide new possibilities for identifying novel molecular targets for the treatment of acute and superficial mucosal injury, mucosal regeneration, and regenerative lesions in the gastrointestinal tract.

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Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage via Akt signaling

Cited by 10 publications

References 37 publications

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

Pathological and therapeutic roles of bioactive peptide trefoil factor 3 in diverse diseases: recent progress and perspective

Mucosal defense: gastroduodenal injury and repair mechanisms

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