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Annual Review of Cell and Developmental... Oct 2019The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A... (Review)
Review
The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A unique feature of the central nervous system (CNS) vasculature is the blood-brain barrier (BBB). The BBB regulates substance influx and efflux to maintain a homeostatic environment for proper brain function. Here, we review the development and cell biology of the BBB, focusing on the cellular and molecular regulation of barrier formation and the maintenance of the BBB through adulthood. We summarize unique features of CNS endothelial cells and highlight recent progress in and general principles of barrier regulation. Finally, we illustrate why a mechanistic understanding of the development and maintenance of the BBB could provide novel therapeutic opportunities for CNS drug delivery.
Topics: Animals; Astrocytes; Basement Membrane; Biological Transport; Blood-Brain Barrier; Brain; Central Nervous System; Endothelial Cells; Homeostasis; Humans; Leukocytes; Neurovascular Coupling; Pericytes; Tight Junctions; Transcytosis; Wnt Signaling Pathway
PubMed: 31299172
DOI: 10.1146/annurev-cellbio-100617-062608 -
Science (New York, N.Y.) Oct 2022We engineered an ultrasensitive reporter of , a biomarker of cellular senescence. Our reporter detected -expressing fibroblasts with certain senescent characteristics...
We engineered an ultrasensitive reporter of , a biomarker of cellular senescence. Our reporter detected -expressing fibroblasts with certain senescent characteristics that appeared shortly after birth in the basement membrane adjacent to epithelial stem cells in the lung. Furthermore, these fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.
Topics: Humans; Basement Membrane; Biomarkers; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Fibroblasts; Inflammation; Lung; Genes, Reporter; Regeneration; Epithelial Cells; Stem Cell Niche
PubMed: 36227993
DOI: 10.1126/science.abf3326 -
German Medical Science : GMS E-journal 2022Since the era when macular hole was considered untreatable, macular hole surgery has come a long way to being one of the most successful surgeries. Internal limiting... (Review)
Review
Since the era when macular hole was considered untreatable, macular hole surgery has come a long way to being one of the most successful surgeries. Internal limiting membrane (ILM) peeling has been an essential step of macular hole surgery since the establishment of the role of ILM in the aetiopathogenesis and progression of macular hole. However, the novel technique was not all virtuous. It had some vices which were not evident immediately. With the advent of spectral domain optical coherence tomography, short- and long-term effects of ILM peeling on macular structures were known; and with microperimetry, its effect on the function of macula could be evaluated. The technique has evolved with time from total peeling to inverted flap to just temporal peeling and temporal flap in an attempt to mitigate its adverse effects and to improve its surgical outcome. ILM abrasion technique and Ocriplasmin may eliminate the need of ILM peeling in selected cases, but they have their own limitations. We here discuss the role of ILM in the pathogenesis of macular hole, the benefits and adverse effects of ILM peeling, and the various modifications of the procedure, to then explore the alternatives.
Topics: Basement Membrane; Epiretinal Membrane; Humans; Retinal Perforations; Retrospective Studies; Treatment Outcome; Visual Acuity; Vitrectomy
PubMed: 35813123
DOI: 10.3205/000309 -
Stroke and Vascular Neurology Jul 2019The blood-brain barrier (BBB) is a highly complex and dynamic structure, mainly composed of brain microvascular endothelial cells, pericytes, astrocytes and the basement... (Review)
Review
The blood-brain barrier (BBB) is a highly complex and dynamic structure, mainly composed of brain microvascular endothelial cells, pericytes, astrocytes and the basement membrane (BM). The vast majority of BBB research focuses on its cellular constituents. Its non-cellular component, the BM, on the other hand, is largely understudied due to its intrinsic complexity and the lack of research tools. In this review, we focus on the role of the BM in BBB integrity. We first briefly introduce the biochemical composition and structure of the BM. Next, the biological functions of major components of the BM in BBB formation and maintenance are discussed. Our goal is to provide a concise overview on how the BM contributes to BBB integrity.
Topics: Animals; Basement Membrane; Blood-Brain Barrier; Capillary Permeability; Collagen Type IV; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Humans; Laminin; Membrane Glycoproteins; Signal Transduction
PubMed: 31338215
DOI: 10.1136/svn-2018-000198 -
Nature Nanotechnology Jan 2024An effective nanotherapeutic transport from the vasculature to the tumour is crucial for cancer treatment with minimal side effects. Here we demonstrate that, in...
An effective nanotherapeutic transport from the vasculature to the tumour is crucial for cancer treatment with minimal side effects. Here we demonstrate that, in addition to the endothelial barrier, the tumour vascular basement membrane surrounding the endothelium acts as a formidable mechanical barrier that entraps nanoparticles (NPs) in the subendothelial void, forming perivascular NP pools. Breaking through this basement membrane barrier substantially increases NP extravasation. Using inflammation triggered by local hyperthermia, we develop a cooperative immunodriven strategy to overcome the basement membrane barrier that leads to robust tumour killing. Hyperthermia-triggered accumulation and inflammation of platelets attract neutrophils to the NP pools. The subsequent movement of neutrophils through the basement membrane can release the NPs entrapped in the subendothelial void, resulting in increased NP penetration into deeper tumours. We show the necessity of considering the tumour vascular basement membrane barrier when delivering nanotherapeutics. Understanding this barrier will contribute to developing more effective antitumour therapies.
Topics: Humans; Basement Membrane; Neoplasms; Neutrophils; Inflammation
PubMed: 37709950
DOI: 10.1038/s41565-023-01498-w -
Metabolism: Clinical and Experimental Jul 2021Laminins are extracellular matrix proteins that reside in the basement membrane and provide structural support in addition to promoting cellular adhesion and migration.... (Review)
Review
Laminins are extracellular matrix proteins that reside in the basement membrane and provide structural support in addition to promoting cellular adhesion and migration. Through interactions with cell surface receptors, laminins stimulate intracellular signaling cascades which direct specific survival and differentiation outcomes. In metabolic tissues such as the pancreas, adipose, muscle, and liver, laminin isoforms are expressed in discrete temporal and spatial patterns suggesting that certain isoforms may support the development and function of particular metabolic cell types. This review focuses on the research to date detailing the expression of laminin isoforms, their potential function, as well as known pathways involved in laminin signaling in metabolic tissues. We will also discuss the current biomedical therapies involving laminins in these tissues in addition to prospective applications, with the goal being to encourage future investigation of laminins in the context of metabolic disease.
Topics: Animals; Basement Membrane; Cell Adhesion; Cell Differentiation; Energy Metabolism; Extracellular Matrix; Humans; Laminin; Metabolic Diseases; Organ Specificity; Signal Transduction
PubMed: 33857525
DOI: 10.1016/j.metabol.2021.154775 -
Essays in Biochemistry Sep 2019Basement membranes (BMs) are specialised extracellular matrix (ECM) structures and collagens are a key component required for BM function. While collagen IV is the major... (Review)
Review
Basement membranes (BMs) are specialised extracellular matrix (ECM) structures and collagens are a key component required for BM function. While collagen IV is the major BM collagen, collagens VI, VII, XV, XVII and XVIII are also present. Mutations in these collagens cause rare multi-systemic diseases but these collagens have also been associated with major common diseases including stroke. Developing treatments for these conditions will require a collective effort to increase our fundamental understanding of the biology of these collagens and the mechanisms by which mutations therein cause disease. Novel insights into pathomolecular disease mechanisms and cellular responses to these mutations has been exploited to develop proof-of-concept treatment strategies in animal models. Combined, these studies have also highlighted the complexity of the disease mechanisms and the need to obtain a more complete understanding of these mechanisms. The identification of pathomolecular mechanisms of collagen mutations shared between different disorders represent an attractive prospect for treatments that may be effective across phenotypically distinct disorders.
Topics: Animals; Basement Membrane; Collagen Diseases; Genetic Therapy; Humans; Mutation; Non-Fibrillar Collagens
PubMed: 31387942
DOI: 10.1042/EBC20180071 -
American Journal of Physiology. Cell... Dec 2022The epidermis is a specialized epithelium that constitutes the outermost layer of the skin, and it provides a protective barrier against environmental assaults.... (Review)
Review
The epidermis is a specialized epithelium that constitutes the outermost layer of the skin, and it provides a protective barrier against environmental assaults. Primarily consisting of multilayered keratinocytes, the epidermis is continuously renewed by proliferation of stem cells and the differentiation of their progeny, which undergo terminal differentiation as they leave the basal layer and move upward toward the surface, where they die and slough off. Basal keratinocytes rest on a basement membrane at the dermal-epidermal junction that is composed of specific extracellular matrix proteins organized into interactive and mechanically supportive networks. Firm attachment of basal keratinocytes, and their dynamic regulation via focal adhesions and hemidesmosomes, is essential for maintaining major skin processes, such as self-renewal, barrier function, and resistance to physical and chemical stresses. The adhesive integrin receptors expressed by epidermal cells serve structural, signaling, and mechanosensory roles that are critical for epidermal cell anchorage and tissue homeostasis. More specifically, the basement membrane components play key roles in preserving the stem cell pool, and establishing cell polarity cues enabling asymmetric cell divisions, which result in the transition from a proliferative basal cell layer to suprabasal cells committed to terminal differentiation. Finally, through a well-regulated sequence of synthesis and remodeling, the components of the dermal-epidermal junction play an essential role in regeneration of the epidermis during skin healing. Here too, they provide biological and mechanical signals that are essential to the restoration of barrier function.
Topics: Epidermis; Epidermal Cells; Basement Membrane; Keratinocytes; Dermis; Cell Differentiation
PubMed: 36374168
DOI: 10.1152/ajpcell.00069.2022 -
Biology Open Aug 2023The basement membrane (BM) is a thin, planar-organized extracellular matrix that underlies epithelia and surrounds most organs. During development, the BM is highly... (Review)
Review
The basement membrane (BM) is a thin, planar-organized extracellular matrix that underlies epithelia and surrounds most organs. During development, the BM is highly dynamic and simultaneously provides mechanical properties that stabilize tissue structure and shape organs. Moreover, it is important for cell polarity, cell migration, and cell signaling. Thereby BM diverges regarding molecular composition, structure, and modes of assembly. Different BM organization leads to various physical features. The mechanisms that regulate BM composition and structure and how this affects mechanical properties are not fully understood. Recent studies show that precise control of BM deposition or degradation can result in BMs with locally different protein densities, compositions, thicknesses, or polarization. Such heterogeneous matrices can induce temporospatial force anisotropy and enable tissue sculpting. In this Review, I address recent findings that provide new perspectives on the role of the BM in morphogenesis.
Topics: Basement Membrane; Morphogenesis; Extracellular Matrix; Cell Movement
PubMed: 37531197
DOI: 10.1242/bio.059980 -
Experimental Eye Research Sep 2020Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene... (Review)
Review
Integrins mediate adhesion of cells to substrates and maintain tissue integrity by facilitating mechanotransduction between cells, the extracellular matrix, and gene expression in the nucleus. Changes in integrin expression in corneal epithelial cells and corneal endothelial cells impacts their adhesion to the epithelial basement membrane (EpBM) and Descemet's membrane, respectively. Integrins also play roles in assembly of basement membranes by both activating TGFβ1 and other growth factors. Over the past two decades, this knowledge has been translated into methods to grow corneal epithelial and endothelial cells in vitro for transplantation in the clinic thereby transforming clinical practice and quality of life for patients. Current knowledge on the expression and function of the integrins that mediate adhesion to the basement membrane expressed by corneal epithelial and endothelial cells in health and disease is summarized. This is the first review to discuss similarities and differences in the integrins expressed by both cell types.
Topics: Basement Membrane; Descemet Membrane; Endothelium, Corneal; Epithelium, Corneal; Extracellular Matrix; Humans; Integrins
PubMed: 32712184
DOI: 10.1016/j.exer.2020.108138