Aspects of the biology of regeneration and repair in the human gastrointestinal tract

Wright, Nicholas

doi:10.1098/rstb.1998.0257

Cited by 64 publications

(43 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During various chronic inflammatory conditions, TFF2 is expressed ectopically in the ulcer-associated cell lineage (28)(29)(30). Furthermore, pathological expression of TFF2 occurs in several metaplastic and neoplastic epithelia (compilations in refs.…”

Section: Tff2 a Muc6-binding Lectin Stabilizing The Gastric Mucus Bamentioning

confidence: 99%

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Hoffmann

2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. The peptide TFF2 (formerly 'spasmolytic polypeptide'), a member of the trefoil factor family (TFF) containing two TFF domains, is mainly expressed together with the mucin MUC6 in the gastric epithelium and duodenal Brunner's glands. Pathologically, TFF2 expression is observed ectopically during stone diseases, chronic inflammatory conditions and in several metaplastic and neoplastic epithelia; most prominent being the 'spasmolytic polypeptide-expressing metaplasia' (SPEM), which is an established gastric precancerous lesion. TFF2 plays a critical role in maintaining gastric mucosal integrity and appears to restrain tumorigenesis in the stomach. Recently, porcine TFF2 has been shown to interact with the gastric mucin MUC6 and thus stabilize the gastric mucus barrier. On the one hand, TFF2 binds to MUC6 via non-covalent lectin interactions with the glycotope GlcNAcα1→4Galβ1→R. On the other hand, TFF2 is probably also covalently bound to MUC6 via disulfide bridges. Thus, implications for the complex multimeric assembly, cross-linking, and packaging of MUC6 as well as the rheology of gastric mucus are discussed in detail in this review. Furthermore, TFF2 is also expressed in minor amounts in the immune and nervous systems. Thus, similar to galectins, its lectin activity would perfectly enable TFF2 to form multivalent complexes and cross-linked lattices with a plethora of transmembrane glycoproteins and thus modulate different signal transduction processes. This could explain the multiple and diverse biological effects of TFF2 [e.g., motogenic, (anti)apoptotic, and angiogenic effects]. Finally, a function during fertilization is also possible for TFF domains because they occur as shuffled modules in certain zona pellucida proteins.

show abstract

Section: Tff2 a Muc6-binding Lectin Stabilizing The Gastric Mucus Bamentioning

confidence: 99%

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Hoffmann

2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…These regulatory peptides, conventionally designated as growth factors and cytokines play an essential role in regulating differential epithelial cell functions in order to preserve normal homeostasis and integrity of the intestinal mucosa [20][21][22][23][24][25] . The terminology of regulatory peptides is often confusing and arbitrary.…”

Section: The Role Of Regulatory Peptides For Intestinal Epithelial Womentioning

confidence: 99%

Epithelial restitution and wound healing in inflammatory bowel disease

Sturm¹,

Dignaß²

2008

WJG

288

260

View full text Add to dashboard Cite

disorders including inflammatory bowel diseases and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface. THE MUCOSAL DEFENSE SYSTEMThe surface of the digestive tract is covered by epithelial cells that constitute an efficient physical barrier between the dietary and enteric flora pathogens found in the intestinal lumen and the individuum, but also allows an exchange between nutrients and the systemic circulation [1] . The epithelial defense mechanism can be categorized into three key components: pre-epithelial, epithelial and post-epithelial, the latter is represented by the lamina propria [2] . The pre-epithelial mucus barrier is composed of mucin associated with other proteins and lipids and forms a continuous gel into which a bicarbonate-rich fluid is secreted, maintaining a neutralizing pH at the epithelial surface. Phosphatidylcholine is the predominant surface bioactive phospholipid found within the gastrointestinal tract [3] . Intestinal epithelial cells secrete mucins and glycocalyx, which contain membrane-anchored negatively charged mucin-like glycoproteins and hydrophobic phospholipids [4] . The tight adherence of mucin to the apical surfaces of epithelia is owed to the existence of the specific complex between mucin oligosaccharides and the mucin binding protein of the apical mucosal membrane [5] . AbstractInflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. S e ve ra l re g u l a t or y pe pt ide fac t or s ac t from t he basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-β-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-β-independent mechanism from...

show abstract

“…Normally, cell renewal takes place continuously in crypts from a proliferating pool of clonal undifferentiated stem cells and cell division is completed in about 24 h. 27 Younger cells migrate up to the villous tips and slough off into the lumen at the extrusion zone. Anti-metabolites, for example cytarabine, are cell cycle-dependent and interfere with the synthesis of DNA in dividing cells whereas the intercalating agents such as the anthracyclines are more effective during the G2 phase after mitosis is complete when the cell has time to restore errors.…”

Section: The Epithelial Phasementioning

confidence: 99%

Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview

Blijlevens¹,

Donnelly²,

Pauw³

2000

Bone Marrow Transplant

236

153

View full text Add to dashboard Cite

Summary:Mucositis is an inevitable side-effect of the conditioning regimens used for haematopoietic stem cell transplantation. The condition is better referred to as mucosal barrier injury (MBI) since it is primarily the result of toxicity and is a complex and dynamic pathobiological process manifested not only in the mouth but also throughout the entire digestive tract. A model has been proposed for oral MBI and consists of four phases, namely inflammatory, epithelial, ulcerative and healing phases. A variety of factors are involved in causing and modulating MBI including the nature of the conditioning regimen, the elaboration of pro-inflammatory and other cytokines, translocation of the resident microflora and their products, for example, endotoxins across the mucosal barrier, exposure to antimicrobial agents and whether or not the haematopoietic stem cell graft is from a donor. Neutropenic typhlitis is the most severe gastrointestinal manifestation of MBI, but it also influences the occurrence of other major transplant-related complications including acute GVHD, veno-occlusive disease and systemic infections. The pathobiology, clinical counterparts and the means of measuring MBI are discussed together with potential approaches for prevention, amelioration and, perhaps, even cure. Bone Marrow Transplantation (2000) 25, 1269-1278. Keywords: mucositis; mucosal barrier injury; diagnosis; risk factors; treatment Mucositis is an inevitable side-effect of the intensive conditioning therapy used for haematopoietic stem cell transplantation 1 and usually refers to the mucosal ulceration of mouth and throat. However, it is generally accepted that oral mucositis is in reality the most obvious manifestation of damage or injury elsewhere particularly that of the gut. Hence, mucosal barrier injury (MBI) may be a more appropriate term for this biological process. There exists no clear definition of MBI which is defined by a constellation of signs and symptoms that vary in their clinical expression. Oral MBI is reported to affect 60% to 100% of transplant recipients 2,3 and is characterised by pain, oedema, erythema, lesions, pseudomembrane formation, excessive mucous production, reduced saliva and bleeding, all of which reduce the patient's ability to eat and drink. In contrast, there are no reliable data on the incidence of gut MBI although intestinal symptoms affect almost every transplant recipient to some extent and include nausea, vomiting, abdominal cramping and watery diarrhoea occasionally accompanied by macroscopic blood loss. The exact course and severity of bowel symptoms of MBI are also difficult to ascertain because many patients are in such pain due to oral MBI that they only gain relief from narcotic analgesia which induces constipation as a result of reduced gut motility. There are also a number of scoring systems for oral MBI 4 although none is universally accepted and all lack standardisation. As yet, there is no system for registering gut MBI although there are published definitions for grading toxicity o...

show abstract

Aspects of the biology of regeneration and repair in the human gastrointestinal tract

Cited by 64 publications

References 65 publications

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more (Review)

Epithelial restitution and wound healing in inflammatory bowel disease

Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview

Contact Info

Product

Resources

About