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Cell Adhesion & Migration 2013Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of... (Review)
Review
Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5) is one of the most widely distributed LM in the developing and mature organism. Its presence in some basement membranes during embryogenesis is absolutely required for maintenance of basement membrane integrity and thus for proper organogenesis. LMα5 also regulates the expression of genes important for major biological processes, in part by repressing or activating signaling pathways, depending upon the physiological context.
Topics: Animals; Basement Membrane; Binding Sites; Body Patterning; Cell Differentiation; Cell Movement; Extracellular Matrix; Gene Expression Regulation, Developmental; Laminin; Mice; Organogenesis; Protein Binding; Stem Cells; Syndecan-4; Wnt Signaling Pathway
PubMed: 23076210
DOI: 10.4161/cam.22236 -
Proceedings of the National Academy of... Feb 2023Lysosomal exocytosis is involved in many key cellular processes but its spatiotemporal regulation is poorly known. Using total internal reflection fluorescence...
Lysosomal exocytosis is involved in many key cellular processes but its spatiotemporal regulation is poorly known. Using total internal reflection fluorescence microscopy (TIRFM) and spatial statistics, we observed that lysosomal exocytosis is not random at the adhesive part of the plasma membrane of RPE1 cells but clustered at different scales. Although the rate of exocytosis is regulated by the actin cytoskeleton, neither interfering with actin or microtubule dynamics by drug treatments alters its spatial organization. Exocytosis events partially co-appear at focal adhesions (FAs) and their clustering is reduced upon removal of FAs. Changes in membrane tension following a hypo-osmotic shock or treatment with methyl-β-cyclodextrin were found to increase clustering. To investigate the link between FAs and membrane tension, cells were cultured on adhesive ring-shaped micropatterns, which allow to control the spatial organization of FAs. By using a combination of TIRFM and fluorescence lifetime imaging microscopy (FLIM), we revealed the existence of a radial gradient in membrane tension. By changing the diameter of micropatterned substrates, we further showed that this gradient as well as the extent of exocytosis clustering can be controlled. Together, our data indicate that the spatial clustering of lysosomal exocytosis relies on membrane tension patterning controlled by the spatial organization of FAs.
Topics: Cell Membrane; Exocytosis; Membranes; Cell Physiological Phenomena; Lysosomes
PubMed: 36800388
DOI: 10.1073/pnas.2207425120 -
Communications Biology Aug 2021The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of...
The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of abdominal anatomy, there are multiple mesenteries. Recent findings point to an alternative model in which digestive organs are connected to a single mesentery. Given that direct evidence of this is currently lacking, we investigated the development and shape of the entire mesentery. Here we confirm that, within the abdomen, there is one mesentery in which all abdominal digestive organs develop and remain connected to. We show that all abdominopelvic organs are organised into two, discrete anatomical domains, the mesenteric and non-mesenteric domain. A similar organisation occurs across a range of animal species. The findings clarify the anatomical foundation of the abdomen; at the foundation level, the abdomen comprises a visceral (i.e. mesenteric) and somatic (i.e. musculoskeletal) frame. The organisation at that level is a fundamental order that explains the positional anatomy of all abdominopelvic organs, vasculature and peritoneum. Collectively, the findings provide a novel start point from which to systemically characterise the abdomen and its contents.
Topics: Humans; Mesentery; Peritoneum
PubMed: 34408242
DOI: 10.1038/s42003-021-02496-1 -
Thorax Jul 1972The history of the investigations into interalveolar communications (pores of Kohn) shows that the question whether they exist and, if so, their nature has for...
The history of the investigations into interalveolar communications (pores of Kohn) shows that the question whether they exist and, if so, their nature has for approximately a century been contentious. The present electron microscopic study of the lungs of mice demonstrates that alveolar pores are normal structures, with edges composed of intact alveolar wall. A number of planes are demonstrated from which a fully compatible reconstruction is made. It is concluded that pores are round or oval structures frequently having at least one type II alveolar cell forming part of their boundary. It is further postulated that pores may be divided by a capillary column stretching across the space, resulting in two openings. A type II alveolar cell forming part of the pore wall may straddle the capillary column. Alveolar macrophages may be found lying free in the pore or lying astride a capillary column. When lying in a corner position type II cells may occupy the full wall thickness and face into three alveoli.
Topics: Animals; Basement Membrane; Capillaries; Epithelial Cells; Macrophages; Male; Mice; Microscopy, Electron; Pulmonary Alveoli
PubMed: 5075613
DOI: 10.1136/thx.27.4.433 -
Mediators of Inflammation 2015Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by... (Review)
Review
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.
Topics: Animals; Bruch Membrane; Carrier Proteins; Humans; Inflammasomes; Macular Degeneration; NLR Family, Pyrin Domain-Containing 3 Protein; Retinal Pigment Epithelium
PubMed: 25698849
DOI: 10.1155/2015/690243 -
Molecules (Basel, Switzerland) Sep 2009Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for... (Review)
Review
Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW) of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nano- and micro-particulate carrier systems will be summarised.
Topics: Administration, Intranasal; Animals; Drug Delivery Systems; Humans; Molecular Weight; Nasal Mucosa; Pharmaceutical Preparations
PubMed: 19783956
DOI: 10.3390/molecules14093754 -
Philosophical Transactions of the Royal... Dec 2022It is fascinating that the amnion and serosa/chorion, two extraembryonic (EE) tissues that are characteristic of the amniote vertebrates (mammals, birds and reptiles),... (Review)
Review
It is fascinating that the amnion and serosa/chorion, two extraembryonic (EE) tissues that are characteristic of the amniote vertebrates (mammals, birds and reptiles), have also independently evolved in insects. In this review, we offer the first detailed, macroevolutionary comparison of EE development and tissue biology across these animal groups. Some commonalities represent independent solutions to shared challenges for protecting the embryo (environmental assaults, risk of pathogens) and supporting its development, including clear links between cellular properties (e.g. polyploidy) and physiological function. Further parallels encompass developmental features such as the early segregation of the serosa/chorion compared to later, progressive differentiation of the amnion and formation of the amniotic cavity from serosal-amniotic folds as a widespread morphogenetic mode across species. We also discuss common developmental roles for orthologous transcription factors and BMP signalling in EE tissues of amniotes and insects, and between EE and cardiac tissues, supported by our exploration of new resources for global and tissue-specific gene expression. This highlights the degree to which general developmental principles and protective tissue features can be deduced from each of these animal groups, emphasizing the value of broad comparative studies to reveal subtle developmental strategies and answer questions that are common across species. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.
Topics: Amnion; Animals; Insecta; Mammals; Morphogenesis; Serous Membrane; Transcription Factors
PubMed: 36252225
DOI: 10.1098/rstb.2021.0268 -
IUBMB Life Apr 2019Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive... (Review)
Review
Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive diffusion process. However, data obtained during the past 15 years showed that its absorption is actually mediated, at least in part, by cholesterol membrane transporters including the scavenger receptor class B type I (SR-BI), CD36 molecule (CD36), NPC1-like transporter 1 (NPC1L1), and ATP-binding cassettes A1 and G1 (ABCA1 and ABCG1). This review focuses on the absorption process of vitamin E across the enterocyte. A special attention is given to the regulation of this process, including the possible competition with other fat-soluble micronutrients, and the modulation of transporter expressions. Overall, recent results noticeably increased the comprehension of vitamin E intestinal transport, but additional investigations are still required to fully appreciate the mechanisms governing vitamin E bioavailability. © 2018 IUBMB Life, 71(4):416-423, 2019.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Animals; Biological Availability; Biological Transport; CD36 Antigens; Chylomicrons; Enterocytes; Humans; Intestinal Absorption; Membrane Transport Proteins; Vitamin E
PubMed: 30308094
DOI: 10.1002/iub.1955 -
Frontiers in Immunology 2021Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced bone remodeling and infection or inflammation are considered central to the pathogenesis of MRONJ. In recent years, increasing evidence has shown that bisphosphonates (BPs)-mediated immunity dysfunction is associated with the pathophysiology of MRONJ. In a healthy state, mucosal immunity provides the first line of protection against pathogens and oral mucosal immune cells defense against potentially invading pathogens by mediating the generation of protective immunoinflammatory responses. In addition, the immune system takes part in the process of bone remodeling and tissue repair. However, the treatment of BPs disturbs the mucosal and osteo immune homeostasis and thus impairs the body's ability to resist infection and repair from injury, thereby adding to the development of MRONJ. Here, we present the current knowledge about immunity dysfunction to shed light on the role of local immune disorder in the development of MRONJ.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Cytokines; Diphosphonates; Disease Susceptibility; Drug-Related Side Effects and Adverse Reactions; Humans; Immunity, Mucosal; Inflammation Mediators; Jaw; Mucous Membrane; Osteogenesis; Osteonecrosis; Signal Transduction; Wound Healing
PubMed: 33717086
DOI: 10.3389/fimmu.2021.606043 -
Biochimica Et Biophysica Acta Sep 2014There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In... (Review)
Review
There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In this review, we discuss the discovery, antiviral activity and mechanism of action of such peptides. While peptide entry inhibitors have been discovered by a wide variety of approaches (structure-based, accidental, intentional, rational and brute force) we show here that they share a common physical chemical property: they are at least somewhat hydrophobic and/or amphipathic and have a propensity to interact with membrane interfaces. We propose that this propensity drives a shared mechanism of action for many peptide entry inhibitors, involving direct interactions with viral and cellular membranes, as well as interactions with the complex hydrophobic protein/lipid interfaces that are exposed, at least transiently, during virus-cell fusion. By interacting simultaneously with the membrane interfaces and other critical hydrophobic surfaces, we hypothesize that peptide entry inhibitors can act by changing the physical chemistry of the membranes, and the fusion protein interfaces bridging them, and by doing so interfere with the fusion of cellular and viral membranes. Based on this idea, we propose that an approach that focuses on the interfacial hydrophobicity of putative entry inhibitors could lead to the efficient discovery of novel, broad-spectrum viral entry inhibitors. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
Topics: Cell Membrane; Genome, Viral; Hydrophobic and Hydrophilic Interactions; Membrane Fusion; Membranes; Peptides; Protein Conformation; Viral Envelope Proteins; Viral Fusion Proteins; Virion
PubMed: 24780375
DOI: 10.1016/j.bbamem.2014.04.015