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Nature Jun 2011Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs... (Review)
Review
Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease. Cellular programs responsible for intestinal homeostasis use diverse intracellular and intercellular networks to promote immune tolerance, inflammation or epithelial restitution. Complex interfaces integrate local host and microbial signals to activate appropriate effector programs selectively and even drive plasticity between these programs. In addition, genetic studies and mouse models have emphasized the role of genetic predispositions and how they affect interactions with microbial and environmental factors, leading to pro-colitogenic perturbations of the host-commensal relationship.
Topics: Animals; Autophagy; Epithelium; Genetic Predisposition to Disease; Humans; Immunity, Innate; Inflammatory Bowel Diseases
PubMed: 21677747
DOI: 10.1038/nature10209 -
Tissue Barriers Oct 2017Formation of tissue barriers starts in early development where it is critical for normal cell fate selection, differentiation and organogenesis. Barrier maintenance is... (Review)
Review
Formation of tissue barriers starts in early development where it is critical for normal cell fate selection, differentiation and organogenesis. Barrier maintenance is critical to the ongoing function of organs during adulthood and aging. Dysfunctional tissue barrier formation and function at any stage of the organismal life cycle underlies many disease states.
Topics: Animals; Cell Differentiation; Claudins; Epithelium; Humans; Tight Junctions
PubMed: 29272190
DOI: 10.1080/21688370.2017.1400866 -
Fertility and Sterility Oct 2016The mesothelium was traditionally thought to be a simple tissue with the sole function of providing a slippery, nonadhesive, and protective surface to allow easy... (Review)
Review
The mesothelium was traditionally thought to be a simple tissue with the sole function of providing a slippery, nonadhesive, and protective surface to allow easy movement of organs within their body cavities. However, our knowledge of mesothelial cell physiology is rapidly expanding, and the mesothelium is now recognized as a dynamic cellular membrane with many other important functions. When injured, mesothelial cells initiate a cascade of processes leading either to complete regeneration of the mesothelium or the development of pathologies such as adhesions. Normal mesothelial healing is unique in that, unlike with other epithelial-like surfaces, healing appears diffusely across the denuded surface, whereas for epithelium healing occurs solely at the wound edges. This is because of a free-floating population of mesothelial cells which attach to the injured serosa. Taking advantage of this phenomenon, intraperitoneal injections of mesothelial cells have been assessed for their ability to prevent adhesion formation. This review discusses some of the functions of mesothelial cells regarding maintenance of serosal integrity and outlines the mechanisms involved in mesothelial healing. In addition, the pathogenesis of adhesion formation is discussed with particular attention to the potential role of mesothelial cells in both preventing and inducing their development.
Topics: Animals; Epithelial Cells; Epithelium; Female; Homeostasis; Humans; Male; Peritoneum; Risk Factors; Signal Transduction; Surgical Procedures, Operative; Tissue Adhesions; Treatment Outcome; Wound Healing
PubMed: 27692285
DOI: 10.1016/j.fertnstert.2016.09.005 -
Nature Communications Mar 2022The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies...
The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Epithelium; Mesothelioma; Mice; Transcription Factors; Zebrafish; Zebrafish Proteins
PubMed: 35354817
DOI: 10.1038/s41467-022-29311-7 -
Insect Biochemistry and Molecular... Dec 2015
Topics: Animals; Epithelium; Insecta
PubMed: 26518152
DOI: 10.1016/j.ibmb.2015.10.013 -
Physiological Reviews Oct 2018The homeoprotein family comprises ~300 transcription factors and was long seen as primarily involved in developmental programs through cell autonomous regulation.... (Review)
Review
The homeoprotein family comprises ~300 transcription factors and was long seen as primarily involved in developmental programs through cell autonomous regulation. However, recent evidence reveals that many of these factors are also expressed in the adult where they exert physiological functions not yet fully deciphered. Furthermore, the DNA-binding domain of most homeoproteins contains two signal sequences allowing their secretion and internalization, thus intercellular transfer. This review focuses on this new-found signaling in cell migration, axon guidance, and cerebral cortex physiological homeostasis and speculates on how it may play important roles in early arealization of the neuroepithelium. It also describes the use of homeoproteins as therapeutic proteins in mouse models of diseases affecting the central nervous system, in particular Parkinson disease and glaucoma.
Topics: Animals; Central Nervous System; Epithelium; Homeodomain Proteins; Humans; Signal Transduction; Transcription Factors
PubMed: 30067157
DOI: 10.1152/physrev.00018.2017 -
Molecules (Basel, Switzerland) Jul 2022Sialyl 6-sulfo Lewis X (6-sulfo sLe) and its derivative sialyl 6-sulfo -acetyllactosamine (LacNAc) are sialylated and sulfated glycans of sialomucins found in the high...
Sialyl 6-sulfo Lewis X (6-sulfo sLe) and its derivative sialyl 6-sulfo -acetyllactosamine (LacNAc) are sialylated and sulfated glycans of sialomucins found in the high endothelial venules (HEVs) of secondary lymphoid organs. A component of 6-sulfo sLe present in the core 1-extended -linked glycans detected by the MECA-79 antibody was previously shown to exist in the lymphoid aggregate vasculature and bronchial mucosa of allergic and asthmatic lungs. The components of 6-sulfo sLe in pulmonary tissues under physiological conditions remain to be analyzed. The CL40 antibody recognizes 6-sulfo sLe and sialyl 6-sulfo LacNAc in -linked and -linked glycans, with absolute requirements for both GlcNAc-6-sulfation and sialylation. Immunostaining of normal mouse lungs with CL40 was performed and analyzed. The contribution of GlcNAc-6--sulfotransferases (GlcNAc6STs) to the synthesis of the CL40 epitope in the lungs was also elucidated. Here, we show that the expression of the CL40 epitope was specifically detected in the mesothelin-positive mesothelium of the pulmonary pleura. Moreover, GlcNAc6ST2 (encoded by ) and GlcNAc6ST3 (encoded by ), but not GlcNAc6ST1 (encoded by ) or GlcNAc6ST4 (encoded by ), are required for the synthesis of CL40-positive glycans in the lung mesothelium. Furthermore, neither GlcNAc6ST2 nor GlcNAc6ST3 is sufficient for in vivo expression of the CL40 epitope in the lung mesothelium, as demonstrated by GlcNAc6ST1/3/4 triple-knock-out and GlcNAc6ST1/2/4 triple-knock-out mice. These results indicate that CL40-positive sialylated and sulfated glycans are abundant in the pleural mesothelium and are synthesized complementarily by GlcNAc6ST2 and GlcNAc6ST3, under physiological conditions in mice.
Topics: Animals; Epithelium; Epitopes; Lewis X Antigen; Mice; Oligosaccharides; Pleura; Polysaccharides; Sialyl Lewis X Antigen; Sulfates
PubMed: 35889417
DOI: 10.3390/molecules27144543 -
The Journal of Allergy and Clinical... Jul 2018Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to... (Review)
Review
Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to esophageal dysfunction. Converging data have placed the esophageal epithelium at the center of disease pathogenesis. In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively. Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology. Additionally, the EoE transcriptome, a set of genes dysregulated in the esophagi of patients with EoE, is enriched in genes that encode for proteins involved in esophageal epithelial cell differentiation. This transcriptome has a high proportion of esophagus-specific epithelial genes that are notable for the unexpected enrichment in genes encoding for proteases and protease inhibitors, as well as in IL-1 family genes, demonstrating a previously unappreciated role for innate immunity responses in the esophagus under homeostatic conditions. Among these pathways, basal production of the serine protease inhibitor, Kazal-type 7 (SPINK7) has been demonstrated to be part of the normal differentiation program of esophageal epithelium. Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic stromal lymphopoietin. Collectively, we put forth a model in which the esophagus is normally equipped as an anti-inflammatory sensing organ and that defects in this pathway, mediated by epithelial protease/protease inhibitor imbalances, unleash inflammatory responses resulting in disorders, such as EoE.
Topics: Eosinophilic Esophagitis; Epithelial Cells; Epithelium; Humans; Peptide Hydrolases; Protease Inhibitors
PubMed: 29980278
DOI: 10.1016/j.jaci.2018.05.008 -
Allergology International : Official... Jan 2018
Topics: Animals; Epithelium; Humans; Hypersensitivity
PubMed: 29291812
DOI: 10.1016/j.alit.2017.12.001 -
Developmental Dynamics : An Official... Mar 2016Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly... (Review)
Review
Coelomic cavities of vertebrates are lined by a mesothelium which develops from the lateral plate mesoderm. During development, the coelomic epithelium is a highly active cell layer, which locally is able to supply mesenchymal cells that contribute to the mesodermal elements of many organs and provide signals which are necessary for their development. The relevance of this process of mesenchymal cell supply to the developing organs is becoming clearer because genetic lineage tracing techniques have been developed in recent years. Body wall, heart, liver, lungs, gonads, and gastrointestinal tract are populated by cells derived from the coelomic epithelium which contribute to their connective and vascular tissues, and sometimes to specialized cell types such as the stellate cells of the liver, the Cajal interstitial cells of the gut or the Sertoli cells of the testicle. In this review we collect information about the contribution of coelomic epithelium derived cells to visceral development, their developmental fates and signaling functions. The common features displayed by all these processes suggest that the epithelial-mesenchymal transition of the embryonic coelomic epithelium is an underestimated but key event of vertebrate development, and probably it is shared by all the coelomate metazoans.
Topics: Animals; Embryo, Mammalian; Epithelium; Humans; Mesoderm; Organogenesis; Signal Transduction; Viscera
PubMed: 26638186
DOI: 10.1002/dvdy.24373