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Special Issue "TFF Peptides: Lectins in Mucosal Protection and More"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 8 October 2019.

Special Issue Editors

Guest Editor
Prof. Dr. Werner Hoffmann Website E-Mail
Director of the Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany
Interests: protection, regeneration and repair of mucous epithelia with special emphasis on the role of TFF peptides; TFF peptides in the immune and central nervous systems
Guest Editor
Prof. Dr. Friedrich Paulsen Website E-Mail
Head of the Institute of Functional and Clinical Anatomy, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Universitätsstr. 19, Erlangen 91054, Germany
Interests: protein and peptide research (mucins, TFF peptides, surfactant proteins, antimicrobial peptides, innate immune system, ocular surface, and lacrimal apparatus)

Special Issue Information

Dear Colleagues,

 

Trefoil factor family (TFF) peptides—together with mucins—are characteristic secretory products of mucous epithelia, where they are involved in different protective mechanisms. For example, they show motogenic and (anti)apoptotic activities. Furthermore, TFFs are also expressed in both the central nervous and immune systems. Pathologically, TFFs are ectopically expressed in various tumors, in inflammatory diseases, and after wounding. Transgenic TFF-deficient mice show different abnormalities in the gastrointestinal tract and the immune system, respectively. Based on these results, TFFs have considerable therapeutic potential, e.g., for treating certain inflammatory disorders as well as oral mucositis after radio- and chemotherapy. Thus far, no high-affinity binding of a TFF peptide with a classical transmembrane receptor has been identified. However, there are numerous interactions of TFFs with (glyco)proteins and a gastrokine documented. The specific interaction particularly of TFF1 and TFF2 with carbohydrate moieties clearly established them as lectins.

Papers submitted to this Special Issue must report high novelty results, e.g., concerning the complex biosynthesis of TFFs, the characterization of TFF interaction partners, the molecular function of TFFs, and the characterization of TFF modules in mosaic proteins. Additionally, state-of-the-art reviews concerning selected functional aspects of TFFs are welcome.

 

Prof. Dr. Werner Hoffmann
Prof. Dr. Friedrich Paulsen
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Apoptosis
  • Cell migration
  • Epithelia
  • Inflammation
  • Lectin
  • Mucin
  • Mucosal protection
  • Neuropeptide
  • TFF domain
  • Trefoil.

Published Papers (5 papers)

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Research

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Open AccessArticle
Effect of Tff3 Deficiency and ER Stress in the Liver
Int. J. Mol. Sci. 2019, 20(18), 4389; https://doi.org/10.3390/ijms20184389 - 06 Sep 2019
Abstract
Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present [...] Read more.
Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3−/−/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism. Full article
(This article belongs to the Special Issue TFF Peptides: Lectins in Mucosal Protection and More)
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Open AccessArticle
Trefoil Factor 3 (TFF3) Is Involved in Cell Migration for Skeletal Repair
Int. J. Mol. Sci. 2019, 20(17), 4277; https://doi.org/10.3390/ijms20174277 - 01 Sep 2019
Abstract
The aim of the study was to explore the possible role of Trefoil Factor Family peptide 3 (TFF3) for skeletal repair. The expression of TFF3 was analyzed in human joint tissues as well as in a murine bone fracture model. Serum levels of [...] Read more.
The aim of the study was to explore the possible role of Trefoil Factor Family peptide 3 (TFF3) for skeletal repair. The expression of TFF3 was analyzed in human joint tissues as well as in a murine bone fracture model. Serum levels of TFF3 following a defined skeletal trauma in humans were determined by ELISA. The mRNA expression of TFF3 was analyzed under normoxia and hypoxia. Expression analysis after stimulation of human mesenchymal progenitor cells (MPCs) with TFF3 was performed by RT2 Profiler PCR Array. The effect of recombinant human (rh)TFF3 on MPCs was analysed by different migration and chemotaxis assays. The effect on cell motility was also visualized by fluorescence staining of F-Actin. TFF3 was absent in human articular cartilage, but strongly expressed in the subchondral bone and periosteum of adult joints. Strong TFF3 immunoreactivity was also detected in murine fracture callus. Serum levels of TFF3 were significantly increased after skeletal trauma in humans. Expression analysis demonstrated that rhTFF3 significantly decreased mRNA of ROCK1. Wound healing assays showed increased cell migration of MPCs by rhTFF3. The F-Actin cytoskeleton was markedly influenced by rhTFF3. Cell proliferation was not increased by rhTFF3. The data demonstrate elevated expression of TFF3 after skeletal trauma. The stimulatory effects on cell motility and migration of MPCs suggest a role of TFF3 in skeletal repair. Full article
(This article belongs to the Special Issue TFF Peptides: Lectins in Mucosal Protection and More)
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Open AccessArticle
p53, miR-34a and EMP1—Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells
Int. J. Mol. Sci. 2019, 20(17), 4129; https://doi.org/10.3390/ijms20174129 - 24 Aug 2019
Abstract
Trefoil factor family peptide 3 (TFF3) is supposed to have tumor suppressive functions in retinoblastoma (RB), but the functional pathway is not completely understood. In the study presented, we investigated the downstream pathway of TFF3 signaling in Y79 RB cells. Results from pG13-luciferase [...] Read more.
Trefoil factor family peptide 3 (TFF3) is supposed to have tumor suppressive functions in retinoblastoma (RB), but the functional pathway is not completely understood. In the study presented, we investigated the downstream pathway of TFF3 signaling in Y79 RB cells. Results from pG13-luciferase reporter assays and western blot analyses indicate induced p53 activity with an upregulation of miR-34a after TFF3 overexpression. Expression levels of the predicted miR-34a target epithelial membrane protein 1 (EMP1) are reduced after TFF3 overexpression. As revealed by WST-1 assay, BrdU, and DAPI cell counts viability and proliferation of Y79 cells significantly decrease following EMP1 knockdown, while apoptosis levels significantly increase. Opposite effects on Y79 cells’ growth could be shown after EMP1 overexpression. Caspase assays showed that EMP1 induced apoptosis after overexpression is at least partially caspase-3/7 dependent. Colony formation and soft agarose assays, testing for anchorage independent growth, revealed that EMP1 overexpressing Y79 cells have a significantly higher ability to form colonies. In in ovo chicken chorioallantoic membrane (CAM) assays inoculated EMP1 overexpressing Y79 cells form significantly larger CAM tumors. Moreover, miR-34a overexpression increases sensitivity of Y79 cells towards RB chemotherapeutics, however, without involvement of EMP1. In summary, the TFF3 signaling pathway in Y79 RB cells involves the activation of p53 with downstream induction of miR-34a and subsequent inhibition of EMP1. Full article
(This article belongs to the Special Issue TFF Peptides: Lectins in Mucosal Protection and More)
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Open AccessArticle
Probiotics Upregulate Trefoil Factors and Downregulate Pepsinogen in the Mouse Stomach
Int. J. Mol. Sci. 2019, 20(16), 3901; https://doi.org/10.3390/ijms20163901 - 10 Aug 2019
Abstract
Probiotics are used in the management of some gastrointestinal diseases. However, little is known about their effects on normal gastric epithelial biology. The aim of this study was to explore how the probiotic mixture VSL#3 affects gastric cell lineages in mice with a [...] Read more.
Probiotics are used in the management of some gastrointestinal diseases. However, little is known about their effects on normal gastric epithelial biology. The aim of this study was to explore how the probiotic mixture VSL#3 affects gastric cell lineages in mice with a special focus on protective and aggressive factors. Weight-matching littermate male mice (n = 14) were divided into treated and control pairs. The treated mice received VSL#3 (5 mg/day/mouse) by gastric gavage for 10 days. Control mice received only the vehicle. Food consumption and bodyweight were monitored. All mice were injected intraperitoneally with bromodeoxyuridine (120 mg/Kg bodyweight) two hours before sacrificed to label S-phase cells. Stomach tissues were processed for lectin- and immunohistochemical examination. ImageJ software was used to quantify immunolabeled gastric epithelial cells. Real-time quantitative polymerase chain reaction was used to provide relative changes in expression of gastric cell lineages specific genes. Results revealed that treated mice acquired (i) increased production of mucus, trefoil factor (TFF) 1 and TFF2, (ii) decreased production of pepsinogen, and (iii) increased ghrelin-secreting cells. No significant changes were observed in bodyweight, food consumption, cell proliferation, or parietal cells. Therefore, VSL#3 administration amplifies specific cell types specialized in the protection of the gastric epithelium. Full article
(This article belongs to the Special Issue TFF Peptides: Lectins in Mucosal Protection and More)
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Review

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Open AccessReview
The Interaction of Helicobacter pylori with TFF1 and Its Role in Mediating the Tropism of the Bacteria Within the Stomach
Int. J. Mol. Sci. 2019, 20(18), 4400; https://doi.org/10.3390/ijms20184400 - 07 Sep 2019
Abstract
Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) [...] Read more.
Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0–6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation. Full article
(This article belongs to the Special Issue TFF Peptides: Lectins in Mucosal Protection and More)
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