Trefoil Factor Family Member 2 (TFF2) as an Inflammatory-Induced and Anti-Inflammatory Tissue Repair Factor

Ghanemi, Abdelaziz; Yoshioka, Mayumi; St‐Amand, Jonny

doi:10.3390/ani10091646

Cited by 9 publications

(11 citation statements)

References 63 publications

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“…Moreover, TFF2 secretion can be regulated by both pro-inflammatory and anti-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), and IL-13, and in turn influence cytokine release and activation (i.e., IL-1, IL-6) [ 69 ], as well as immune cell recruitment [ 73 ]. This correlates with its suggested roles both as anti-inflammatory [ 74 ] and in reducing immune-mediated damage [ 75 ].…”

Section: Tff2 Metabolic Properties and Implicationssupporting

confidence: 53%

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

Ghanemi

Yoshioka²,

St‐Amand

2021

Metabolites

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Obesity has its epidemiological patterns continuously increasing. With controlling both diet and exercise being the main approaches to manage the energy metabolism balance, a high-fat (HF) diet is of particular importance. Indeed, lipids have a low satiety potential but a high caloric density. Thus, focusing on pharmacologically targetable pathways remains an approach with promising therapeutic potential. Within this context, trefoil factor family member 2 (Tff2) has been characterized as specifically induced by HF diet rather than low-fat diet. TFF2 has also been linked to diverse neurological mechanisms and metabolic patterns suggesting its role in energy balance. The hypothesis is that TFF2 would be a HF diet-induced signal that regulates metabolism with a focus on lipids. Within this review, we put the spotlight on key findings highlighting this line of thought. Importantly, the hypothetical mechanisms pointed highlight TFF2 as an important contributor to obesity development via increasing lipids intestinal absorption and anabolism. Therefore, an outlook for future experimental activities and evaluation of the therapeutic potential of TFF2 inhibition is given. Indeed, its knockdown or downregulation would contribute to an antiobesity phenotype. We believe this work represents an addition to our understanding of the lipidic molecular implications in obesity, which will contribute to develop therapies aiming to manage the lipidic metabolic pathways including the absorption, storage and metabolism via targeting TFF2-related pathways. We briefly discuss important relevant concepts for both basic and clinical researchers.

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Section: Tff2 Metabolic Properties and Implicationssupporting

confidence: 53%

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

Ghanemi

Yoshioka²,

St‐Amand

2021

Metabolites

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“…This possibility is supported by the over-detection in faecal samples containing SARS-CoV-2 RNA of trefoil factor family peptides. These essential proteins are involved in protection and repair of the gastrointestinal tract 33 . This response suggests that expression of TFF variants could be used to predict prognosis, or to monitor therapeutic e cacy.…”

Section: Discussionmentioning

confidence: 99%

Taxonomical and functional changes in COVID-19 faecal microbiome are related to SARS-CoV-2 faecal load

Armengaud

Grenga

Pible³

et al. 2021

Preprint

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Since the beginning of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the gastro-intestinal (GI) tract has emerged as an important organ influencing the propensity to and potentially severity of the related COVID-19 disease. However, the contribution of the SARS-CoV-2 intestinal infection on COVID-19 pathogenesis remains to be clarified. In this exploratory study, we evidenced that alterations in the composition of the gut microbiota depends on the levels of SARS-CoV-2 RNA in the gastrointestinal tract but not on the presence of SARS-CoV-2 in the respiratory tract, COVID-19 severity and GI symptoms. Altered molecular functions in the microbiota profiles of high SARS-CoV-2 RNA level faeces as established by metaproteomics highlight mechanisms that may contribute to vicious cycles. Uncovering the role of this gut microbiota dysbiosis could drive the investigation of alternative therapeutic strategies to favour the clearance of the virus and potentially mitigate the effect of SARS-CoV-2 infection.

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“…In contrast to TFF1, TFF2 was only transiently reduced in the human stomach after H. pylori infection [ 83 ]. TFF2 is rather up-regulated in inflammatory conditions as shown for various diseases [ 107 ], as well as in murine models of gastric inflammation [ 88 ] and allergic airway disease [ 108 ]. For example, gastrin-deficient mice exhibit chronic inflammation in the hypochlorhydric stomach and the Th1 cytokine interferon-gamma (IFN-γ) is the most abundant pro-inflammatory cytokine [ 109 ].…”

Section: Regulation Of Tff Expression By Inflammatory Mediatorsmentioning

confidence: 99%

“…This explains why Tff2 KO mice have a compromised immune system [ 15 ]. On the one hand, TFF2 is a brake for myeloid cells (e.g., inhibition of IL-6 and IL-12 release) so that, in particular, Th1 inflammation after a mucosal challenge (infection) is not overshooting (anti-inflammatory effect; Figure 3 ) [ 16 , 18 , 107 , 153 ]. On the other hand, TFF2 is a positive regulator of the alarmin IL-33 in the CNS and mucous epithelia, which is an activator of a Th2 immune response after injury ( Figure 3 ) [ 158 , 159 ].…”

Section: Role Of Tff Peptides For Inflammatory Processesmentioning

confidence: 99%

Trefoil Factor Family (TFF) Peptides and Their Links to Inflammation: A Re-evaluation and New Medical Perspectives

Hoffmann

2021

IJMS

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Trefoil factor family peptides (TFF1, TFF2, TFF3), together with mucins, are typical exocrine products of mucous epithelia. Here, they act as a gastric tumor suppressor (TFF1) or they play different roles in mucosal innate immune defense (TFF2, TFF3). Minute amounts are also secreted as endocrine, e.g., by the immune and central nervous systems. As a hallmark, TFF peptides have different lectin activities, best characterized for TFF2, but also TFF1. Pathologically, ectopic expression occurs during inflammation and in various tumors. In this review, the role of TFF peptides during inflammation is discussed on two levels. On the one hand, the expression of TFF1-3 is regulated by inflammatory signals in different ways (upstream links). On the other hand, TFF peptides influence inflammatory processes (downstream links). The latter are recognized best in various Tff-deficient mice, which have completely different phenotypes. In particular, TFF2 is secreted by myeloid cells (e.g., macrophages) and lymphocytes (e.g., memory T cells), where it modulates immune reactions triggering inflammation. As a new concept, in addition to lectin-triggered activation, a hypothetical lectin-triggered inhibition of glycosylated transmembrane receptors by TFF peptides is discussed. Thus, TFFs are promising players in the field of glycoimmunology, such as galectins and C-type lectins.

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Trefoil Factor Family Member 2 (TFF2) as an Inflammatory-Induced and Anti-Inflammatory Tissue Repair Factor

Cited by 9 publications

References 63 publications

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

Trefoil Factor Family Member 2: From a High-Fat-Induced Gene to a Potential Obesity Therapy Target

Taxonomical and functional changes in COVID-19 faecal microbiome are related to SARS-CoV-2 faecal load

Trefoil Factor Family (TFF) Peptides and Their Links to Inflammation: A Re-evaluation and New Medical Perspectives

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