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Bioscience Reports Jan 2022Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of... (Review)
Review
Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors (TFs) including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT TFs and discussed their role in the process. We have also tried to focus on their mechanism of action, their interdependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type-dependent manner.
Topics: Animals; Antifibrotic Agents; Antineoplastic Agents; Embryonic Development; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Humans; Neoplasms; Phenotype; Signal Transduction; Transcription Factors; Wound Healing
PubMed: 34708244
DOI: 10.1042/BSR20211754 -
The Journal of Clinical Investigation Jun 2009The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly... (Review)
Review
The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
Topics: Animals; Cell Differentiation; Epithelial Cells; Fibrosis; Humans; Mesenchymal Stem Cells; Neoplasms; Regeneration
PubMed: 19487818
DOI: 10.1172/JCI39104 -
Cell Reports Feb 2019Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the...
Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it is enclosed within the spheroid. We developed a technique to reverse enteroid polarity such that the apical surface everts to face the media. Apical-out enteroids maintain proper polarity and barrier function, differentiate into the major intestinal epithelial cell (IEC) types, and exhibit polarized absorption of nutrients. We used this model to study host-pathogen interactions and identified distinct polarity-specific patterns of infection by invasive enteropathogens. Salmonella enterica serovar Typhimurium targets IEC apical surfaces for invasion via cytoskeletal rearrangements, and Listeria monocytogenes, which binds to basolateral receptors, invade apical surfaces at sites of cell extrusion. Despite different modes of entry, both pathogens exit the epithelium within apically extruding enteroid cells. This model will enable further examination of IECs in health and disease.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Polarity; Epithelial Cells; Fatty Acids; Host-Pathogen Interactions; Humans; Intestinal Mucosa; Listeria monocytogenes; Models, Biological; Salmonella typhimurium; Spheroids, Cellular
PubMed: 30811997
DOI: 10.1016/j.celrep.2019.01.108 -
Cell Host & Microbe May 2015Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide...
Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut.
Topics: Animals; Bacteria; Cell Line; Epithelial Cells; Fatty Acids, Volatile; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1; Mice; Oxygen Consumption
PubMed: 25865369
DOI: 10.1016/j.chom.2015.03.005 -
Current Opinion in Immunology Feb 2020The surface and lining tissues of our body are exposed to the external environment, and as such these epithelial tissues must form structural barriers able to defend... (Review)
Review
The surface and lining tissues of our body are exposed to the external environment, and as such these epithelial tissues must form structural barriers able to defend against microbes, environmental toxins, and mechanical stress. Their cells are equipped to detect a diverse array of surface perturbations, and then launch signaling relays to the immune system. The aim of these liaisons is to coordinate the requisite immune cell response needed to preserve and/or restore barrier integrity and defend the host. It has been recently appreciated that epithelial cells learn from these experiences. Following inflammatory exposure, long-lived stem cells within the tissue retain an epigenetic memory that endows them with heightened responsiveness to subsequent encounters with stress. Here, we review the recent literature on how epithelial cells sense signals from microbes, allergens, and injury at the tissue surface, and transmit this information to immune cells, while embedding a memory of the experience within their chromatin.
Topics: Animals; Epithelial Cells; Humans
PubMed: 31874430
DOI: 10.1016/j.coi.2019.11.004 -
European Cells & Materials Aug 2019Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching... (Review)
Review
Epithelium attachment to the tooth or abutment surface is necessary to form a biological seal preventing pathogens and irritants from penetrating the body and reaching the underlying soft tissues and bone, which in turn can lead to inflammation and subsequent bone resorption. The present review investigated oral wound closure and the role of micro-environment, saliva, crevicular fluid and microbiota in wound healing. The importance of the junctional epithelium (peri-implant epithelium) attachment to the abutment surface was investigated. Current research focuses on macro-design, surface-topography, surface-chemistry, materials, coatings and wettability to enhance attachment, since these optimised surface properties are expected to promote keratinocyte attachment and spreading through hemi-desmosome formation. Detailed studies describing the extent of junctional epithelium attachment - e.g. barrier function, hemi-desmosomes, epithelium quality, composition of the external basement membrane or ability of the epithelium to resist microbial penetration and colonisation - are not yet reported in animals due to ethical considerations, scalability, expense, technical challenges and limited availability of antibodies. In vitro studies generally include relatively simple 2D culture models, which lack the complexity required to draw relevant conclusions. Additionally, human organotypic 3D mucosa models are being developed. The present review concluded that more research using these organotypic mucosa models may identify relevant parameters involved in soft-tissue-abutment interactions, which could be used to study different macro-shapes and surface modifications. Such studies would bridge the gap between clinical, animal and traditional in vitro cell culture studies supporting development of abutments aiming at improved clinical performance.
Topics: Animals; Cell Adhesion; Dental Abutments; Epithelial Cells; Gingiva; Humans; Wound Healing
PubMed: 31410840
DOI: 10.22203/eCM.v038a06 -
Frontiers in Immunology 2022
Topics: Epithelial Cells; Stem Cells
PubMed: 36059545
DOI: 10.3389/fimmu.2022.1003490 -
Cells Sep 2021Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel... (Review)
Review
Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel proteins in cell types and tissues in addition to the nervous system, such as epithelia, where they have been little studied, and their role has remained elusive. Dynamic epithelia are intrinsically exposed to mechanical forces. A response to pull and push is assumed to constitute an essential part of morphogenetic movements of epithelial tissues, for example. Mechano-gated channels may participate in sensing and responding to such forces. In this review, focusing on , we highlight recent results that will guide further investigations concerned with the mechanistic role of these ion channels in epithelial cells.
Topics: Animals; Epithelial Cells; Humans; Ion Channel Gating; Ion Channels; Mechanotransduction, Cellular; Morphogenesis
PubMed: 34571929
DOI: 10.3390/cells10092280 -
Physical Biology Jan 2019The transition of epithelial cells into a mesenchymal state (epithelial-to-mesenchymal transition or EMT) is a highly dynamic process implicated in various biological... (Review)
Review
The transition of epithelial cells into a mesenchymal state (epithelial-to-mesenchymal transition or EMT) is a highly dynamic process implicated in various biological processes. During EMT, cells do not necessarily exist in 'pure' epithelial or mesenchymal states. There are cells with mixed (or hybrid) features of the two, which are termed as the intermediate cell states (ICSs). While the exact functions of ICS remain elusive, together with EMT it appears to play important roles in embryogenesis, tissue development, and pathological processes such as cancer metastasis. Recent single cell experiments and advanced mathematical modeling have improved our capability in identifying ICS and provided a better understanding of ICS in development and disease. Here, we review the recent findings related to the ICS in/or EMT and highlight the challenges in the identification and functional characterization of ICS.
Topics: Animals; Cell Differentiation; Embryonic Development; Epithelial Cells; Epithelial-Mesenchymal Transition; Humans
PubMed: 30560804
DOI: 10.1088/1478-3975/aaf928 -
European Journal of Cell Biology Jan 2019Cell polarity identifies the asymmetry of a cell. Various types of cells, including odontoblasts and epithelial cells, polarize to fulfil their destined functions.... (Review)
Review
Cell polarity identifies the asymmetry of a cell. Various types of cells, including odontoblasts and epithelial cells, polarize to fulfil their destined functions. Odontoblast polarization is a prerequisite and fundamental step for tooth development and tubular dentin formation. Current knowledge of odontoblast polarization, however, is very limited, which greatly impedes the development of novel approaches for regenerative endodontics. Compared to odontoblasts, epithelial cell polarization has been extensively studied over the last several decades. The knowledge obtained from epithelia polarization has been found applicable to other cell types, which is particularly useful considering the remarkable similarities of the morphological and compositional features between polarized odontoblasts and epithelia. In this review, we first discuss the characteristics, the key regulatory factors, and the process of epithelial polarity. Next, we compare the known facts of odontoblast polarization with epithelial cells. Lastly, we clarify knowledge gaps in odontoblast polarization and propose the directions for future research to fill the gaps, leading to the advancement of regenerative endodontics.
Topics: Animals; Cell Polarity; Epithelial Cells; Models, Biological; Odontoblasts; rho GTP-Binding Proteins
PubMed: 30473389
DOI: 10.1016/j.ejcb.2018.11.003