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Science (New York, N.Y.) Jan 2023The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that...
The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport.
Topics: Animals; Humans; Mice; Dura Mater; Endothelium; Subarachnoid Space; Epithelium; Brain; Cerebrospinal Fluid
PubMed: 36603070
DOI: 10.1126/science.adc8810 -
Critical Reviews in Toxicology Apr 1982The origins, nature, and reactions of the mesothelium have intrigued investigators for over 100 years. Recently, the use of sophisticated techniques has clarified... (Review)
Review
The origins, nature, and reactions of the mesothelium have intrigued investigators for over 100 years. Recently, the use of sophisticated techniques has clarified earlier impressions of its development, structure, and function. The structure of mesothelium reflects its functional properties, its long slender microvilli entrapping a layer of glycosoaminoglycans, providing a frictionless free surface between the parietal and visceral serosa. Transport requirements are met by various surface modifications and both inter- and intra-cellular mechanisms occur. The presence of stomatal openings in the mesothelial membrane has been established, and they may have a major role to play in the movement of cells to and from the serosal cavities. In addition, mesothelial cells can respond to situations of increased functional demand and during the course of inflammation, the mesothelium's fibrinolytic properties are of major importance in preventing the formation of adhesions and the enhancement of healing. Of all the unanswered questions the most significant is the nature, localization, and potentialities of mesothelial precursors. A mesodermal origin is readily acknowledged, but the healing process of damaged mesothelium is less clear. It seems probable that "mature" mesothelium is one source of cell renewal, but mesenchymal cells located in the submesothelial serosa are also strong contenders. Neoplastic mesothelium can adopt a spectrum of histological appearances, reflecting its mesodermal origins. In fact, overacceptance of this concept has erroneously led to the classification of other neoplasms arising in the serosal area as mesotheliomas. Although the ocogenic sequence is still obscure, asbestos is recognized as the major etiologic agent in malignant mesotheliomas. In 1955, Hartwell described differing impressions of the peritoneum as seen through the eyes of an anatomist, an histologist, and a surgeon. In this review on the mesothelium we have attempted to unravel some of its complexities as viewed by embryologists, electronmicroscopists, cell biologists, pathologists, and oncologists.
Topics: Biological Transport; Cell Division; Cells, Cultured; Endothelium; Humans; Inflammation; Intercellular Junctions; Mesothelioma; Wound Healing
PubMed: 7044686
DOI: 10.3109/10408448209041321 -
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 -
Pharmacological Research Mar 2019Much research now indicates that vagal nerve stimulation results in a systemic reduction in inflammatory cytokine production and an increase in anti-inflammatory cell... (Review)
Review
Much research now indicates that vagal nerve stimulation results in a systemic reduction in inflammatory cytokine production and an increase in anti-inflammatory cell populations that originates from the spleen. Termed the 'cholinergic anti-inflammatory pathway', therapeutic activation of this innate physiological response holds enormous promise for the treatment of inflammatory disease. Much controversy remains however, regarding the underlying physiological pathways mediating this response. This controversy is anchored in the fact that the vagal nerve itself does not innervate the spleen. Recent research from our own laboratory indicating that oral intake of sodium bicarbonate stimulates splenic anti-inflammatory pathways, and that this effect may require transmission of signals to the spleen through the mesothelium, provide new insight into the physiological pathways mediating the cholinergic anti-inflammatory pathway. In this review, we examine proposed models of the cholinergic anti-inflammatory pathway and attempt to frame our recent results in relation to these hypotheses. Following this discussion, we then provide an alternative model of the cholinergic anti-inflammatory pathway which is consistent both with our recent findings and the published literature. We then discuss experimental approaches that may be useful to delineate these hypotheses. We believe the outcome of these experiments will be critical in identifying the most appropriate methods to harness the therapeutic potential of the cholinergic anti-inflammatory pathway for the treatment of disease and may also shed light on the etiology of other pathologies, such as idiopathic fibrosis.
Topics: Acetylcholine; Animals; Epithelium; Humans; Inflammation; Kidney; Neuroimmunomodulation; Spleen; T-Lymphocytes; Vagus Nerve
PubMed: 30616018
DOI: 10.1016/j.phrs.2019.01.007 -
Ageing Research Reviews May 2018Human peritoneal mesothelial cells belong to a narrow group of somatic cells in which both the triggers and the mechanisms of senescence have already been well defined.... (Review)
Review
Human peritoneal mesothelial cells belong to a narrow group of somatic cells in which both the triggers and the mechanisms of senescence have already been well defined. Importantly, senescent mesothelial cells have been found in the peritoneal cavity in vivo. From a clinical point of view, peritoneal mesothelial cells have been recognized as playing a critical role in the intraperitoneal development of tumor metastases. The pro-cancerogenic behavior of mesothelial cells is even more pronounced when the cells exhaust their proliferative capacity and become senescent. In this review, we summarize the current state of art regarding the contribution of peritoneal mesothelial cells in the progression of ovarian, colorectal, and pancreatic carcinomas, with particular attention paid to the cancer-promoting activity of their senescent counterparts. Moreover, we delineate the mechanisms, mediators, and signaling pathways that are engaged by the senescent mesothelial cells to support such vital elements of cancer progression as adhesion, proliferation, migration, invasion, epithelial-mesenchymal transition, and angiogenesis. Finally, we discuss the experimental evidence regarding both natural and synthetic compounds that may either prevent or restrict cancer development by delaying senescence of mesothelial cells.
Topics: Animals; Cellular Senescence; Disease Progression; Epithelium; Humans; Neovascularization, Pathologic; Peritoneal Cavity; Peritoneal Neoplasms; Peritoneum; Signal Transduction
PubMed: 29355719
DOI: 10.1016/j.arr.2018.01.002 -
American Journal of Physiology. Lung... May 2019
Topics: Epithelium; Heart
PubMed: 30838864
DOI: 10.1152/ajplung.00082.2019 -
The International Journal of Artificial... Jun 2007Bichat first described the mesothelium in 1827 but despite its early discovery, it has only been in recent years that its importance both in health and disease has been... (Review)
Review
Bichat first described the mesothelium in 1827 but despite its early discovery, it has only been in recent years that its importance both in health and disease has been realised. One area still poorly understood is that of the mechanisms regulating mesothelial repair. Mesothelial cells are derived from the mesoderm but express many epithelial characteristics. However, mesothelium does not heal in the same way as other epithelial-like cells. Epithelium heals by centripetal migration, with cells at the edge of the wound proliferating and migrating into the injured area. Hertzler in 1919 noted that both large and small peritoneal injuries healed within the same time frame, concluding that the mesothelium could not heal solely by centripetal migration. The exact mechanisms involved in mesothelial regeneration following injury are controversial with a number of proposals suggested to explain the origin of the regenerating cells. This review will examine these proposals and give some insights into the likely mechanisms involved.
Topics: Animals; Cell Count; Cell Differentiation; Cell Division; Cells, Cultured; Epithelium; Humans; Peritoneum; Regeneration; Serous Membrane; Wound Healing
PubMed: 17628849
DOI: 10.1177/039139880703000606 -
Peritoneal Dialysis International :... 1995Substantial derangements of mesothelial biology are observed during experimental simulations of dialysis conditions, inferred from the content of human dialysis effluent... (Review)
Review
Substantial derangements of mesothelial biology are observed during experimental simulations of dialysis conditions, inferred from the content of human dialysis effluent and visualized by microscopy of human mesothelial biopsies. Can osmotically active solutions be made biocompatible with the osmoregulatory system of the mesothelium? Can the contributions of the mesothelium to host defenses against inflammation and/or infection be supported during CAPD? Do underlying metabolic derangements present in various kidney diseases and end-stage renal disease, regardless of cause, require customized CAPD protocols and solutions? Use of dialysis solutions less directly toxic to the mesothelium is a necessary step toward some day manipulating peritoneal biology by pharmacological and therapeutic modalities.
Topics: Cytotoxins; Epithelial Cells; Epithelium; Humans; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Phosphatidylcholines; Prostaglandins
PubMed: 8555322
DOI: No ID Found -
American Journal of Clinical Pathology May 2021Peritoneal mesothelial cysts have been reported under various terms, including benign cystic mesothelioma, usually in the form of case reports/series, whereas...
OBJECTIVES
Peritoneal mesothelial cysts have been reported under various terms, including benign cystic mesothelioma, usually in the form of case reports/series, whereas extraperitoneal cases are rarely reported. Our objective was to report the detailed characteristics of cystic lesions of the serosal cavities.
METHODS
We retrospectively examined the clinicopathologic findings of a series of mesothelial cystic lesions (n = 79).
RESULTS
Most cases (n = 68, 86%) concerned the peritoneum, whereas 11 (14%) concerned the pericardium. No pleural cases were found. A total of 51 (64.5%) lesions were solitary, whereas 28 (35.5%) were multiple. Peritoneal lesions harbored a plump eosinophilic mesothelium and a loose connective stroma, whereas pericardial lesions showed a cuboidal/flattened mesothelium, collagenous stroma, intense inflammation, and other tissue types, like adipose and muscle tissue. Solitary peritoneal lesions are usually extrapelvic and found in older patients incidentally during other surgeries, whereas multiple lesions are found in younger patients and usually in the pelvis. The lesions show a benign clinical course with rare recurrences but no malignant transformation.
CONCLUSIONS
Most mesothelial cysts are peritoneal and rarely pericardial. Peritoneal cysts differ from pericardial cysts. Peritoneal solitary lesions differ from multiple lesions, also suggesting their pathogenetic differences.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cysts; Epithelium; Humans; Male; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Pelvis; Pleura; Retrospective Studies; Young Adult
PubMed: 33258870
DOI: 10.1093/ajcp/aqaa189 -
Albumin transcytosis in mesothelium: further evidence of a transcellular pathway in polarized cells.American Journal of Physiology. Lung... Jan 2002
Review
Topics: Albumins; Animals; Cell Polarity; Epithelial Cells; Epithelium; Humans
PubMed: 11741809
DOI: 10.1152/ajplung.00406.2001