Matrix Biology Plus最新文献

{"title":"Matritecture: Mapping the extracellular matrix architecture during health and disease","authors":"Raphael Reuten ,&nbsp;Alejandro E. Mayorca-Guiliani ,&nbsp;Janine Terra Erler","doi":"10.1016/j.mbplus.2022.100102","DOIUrl":"10.1016/j.mbplus.2022.100102","url":null,"abstract":"<div><p>All cells in multicellular organisms are housed in the extracellular matrix (ECM), an acellular edifice built up by more than a thousand proteins and glycans. Cells engage in a reciprocal relationship with the ECM; they build, inhabit, maintain, and remodel the ECM, while, in turn, the ECM regulates their behavior. The homeostatic balance of cell-ECM interactions can be lost, due to ageing, irritants or diseases, which results in aberrant cell behavior. The ECM can suppress or promote disease progression, depending on the information relayed to cells. Instructions come in the form of biochemical (e.g., composition), biophysical (e.g., stiffness), and topographical (e.g., structure) cues. While advances have been made in many areas, we only have a very limited grasp of ECM topography. A detailed atlas deciphering the spatiotemporal arrangement of all ECM proteins is lacking. We feel that such an extracellular matrix architecture (matritecture) atlas should be a priority goal for ECM research. In this commentary, we will discuss the need to resolve the spatiotemporal matritecture to identify potential disease triggers and therapeutic targets and present strategies to address this goal. Such a detailed matritecture atlas will not only identify disease-specific ECM structures but may also guide future strategies to restructure disease-related ECM patterns reverting to a normal pattern.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000023/pdfft?md5=4867ac2b65d82003466b4ffbd978420f&pid=1-s2.0-S2590028522000023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42489418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunosuppressive glycoproteins associate with breast tumor fibrosis and aggression","authors":"Kevin James Metcalf ,&nbsp;Mary-Kate Hayward ,&nbsp;Eric Berens ,&nbsp;Alastair J. Ironside ,&nbsp;Connor Stashko ,&nbsp;E. Shelley Hwang ,&nbsp;Valerie M. Weaver","doi":"10.1016/j.mbplus.2022.100105","DOIUrl":"10.1016/j.mbplus.2022.100105","url":null,"abstract":"<div><p>Tumors feature elevated sialoglycoprotein content. Sialoglycoproteins promote tumor progression and are linked to immune suppression via the sialic acid-Siglec axis. Understanding factors that increase sialoglycoprotein biosynthesis in tumors could identify approaches to improve patient response to immunotherapy. We quantified higher levels of sialoglycoproteins in the fibrotic regions within human breast tumor tissues. Human breast tumor subtypes, which are more fibrotic, similarly featured increased sialoglycoprotein content. Further analysis revealed the breast cancer cells as the primary cell type synthesizing and secreting the tumor tissue sialoglycoproteins and confirmed that the more aggressive, fibrotic breast cancer subtypes expressed the highest levels of sialoglycoprotein biosynthetic genes. The more aggressive breast cancer subtypes also featured greater infiltration of immunosuppressive <em>SIGLEC7</em>, <em>SIGLEC9</em>, and <em>SIGLEC10</em>-pos myeloid cells, indicating that triple-negative breast tumors had higher expression of both immunosuppressive Siglec receptors and their cognate ligands. The findings link sialoglycoprotein biosynthesis and secretion to tumor fibrosis and aggression in human breast tumors. The data suggest targeting of the sialic acid-Siglec axis may comprise an attractive therapeutic target particularly for the more aggressive HER2+ and triple-negative breast cancer subtypes.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/26/main.PMC8981759.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting repair of the vascular endothelium and glycocalyx after traumatic injury with plasma and platelet resuscitation","authors":"Mark Barry ,&nbsp;Shibani Pati","doi":"10.1016/j.mbplus.2022.100107","DOIUrl":"10.1016/j.mbplus.2022.100107","url":null,"abstract":"<div><p>Severely injured patients with hemorrhagic shock can develop endothelial dysfunction, systemic inflammation, and coagulation disturbances collectively known as the endotheliopathy of trauma (EOT). Shedding of the endothelial glycocalyx occurs early after injury, contributes to breakdown of the vascular barrier, and plays a critical role in the pathogenesis of multiple organ dysfunction, leading to poor outcomes in trauma patients. In this review we discuss (i) the pathophysiology of endothelial glycocalyx and vascular barrier breakdown following hemorrhagic shock and trauma, and (ii) the role of plasma and platelet transfusion in maintaining the glycocalyx and vascular endothelial integrity.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100107"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000072/pdfft?md5=52a7d432cad7e1a398aee29f07665d05&pid=1-s2.0-S2590028522000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46357553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promotes hyaluronan-dependent leukocyte adhesion and inflammatory cytokine expression in vitro","authors":"Inkyung Kang ,&nbsp;Christian Hundhausen ,&nbsp;Stephen P. Evanko ,&nbsp;Prasanthi Malapati ,&nbsp;Gail Workman ,&nbsp;Christina K. Chan ,&nbsp;Cliff Rims ,&nbsp;Gary S. Firestein ,&nbsp;David L. Boyle ,&nbsp;Kevin M. MacDonald ,&nbsp;Jane H. Buckner ,&nbsp;Thomas N. Wight","doi":"10.1016/j.mbplus.2022.100110","DOIUrl":"10.1016/j.mbplus.2022.100110","url":null,"abstract":"<div><p>The content and organization of hyaluronan (HA) in the extracellular matrix (ECM) have been identified as strong indicators of inflammation in joint disease, although the source and role of HA as an effector of inflammation is not clear. In this study, we established co-cultures of activated human CD4 T cells with fibroblast-like synoviocytes (FLS) from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects and examined the role of HA in promoting inflammatory events. Co-cultures of RA FLS with activated CD4 T cells generated an HA-enriched ECM that promoted enhanced monocyte adhesion compared to co-cultures of OA FLS with activated CD4 T cells. In addition, both OA FLS and RA FLS co-cultures with activated CD4 T cells elicited significant increases in the expression of IL1β, TNF, and IL6, with the increase in IL6 expression most prominent in RA co-cultures. Blocking HA synthesis and accumulation with 4-methylumbelliferone reduced expression of IL6, IL1β, and TNF in both OA FLS and RA FLS co-cultures. The increase in HA synthesis in the co-cultures was mimicked by IL6 trans-signaling of FLS in the absence of CD4 T cells. Inhibition of HA synthesis blocked the increase in IL6 by RA FLS mediated by IL6 trans-signaling, suggesting that the HA synthetic pathway may be a key mediator in IL6 expression by FLS. Overall, our study indicates that HA-enriched ECM generated by co-cultures of activated CD4 T cells with FLS from human joints creates a pathogenic microenvironment by promoting adhesion of leukocytes and expression of inflammatory cytokines including IL6.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000102/pdfft?md5=4b285ca38d680db3f24121b99aaee448&pid=1-s2.0-S2590028522000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42406233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The endothelial glycocalyx in critical illness: A pediatric perspective","authors":"Robert P. Richter ,&nbsp;Gregory A. Payne ,&nbsp;Namasivayam Ambalavanan ,&nbsp;Amit Gaggar ,&nbsp;Jillian R. Richter","doi":"10.1016/j.mbplus.2022.100106","DOIUrl":"10.1016/j.mbplus.2022.100106","url":null,"abstract":"<div><p>The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000060/pdfft?md5=1c3ba82921cc9134904aa17c7f70e94a&pid=1-s2.0-S2590028522000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48478468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model","authors":"Weikun Xiao ,&nbsp;Mahsa Pahlavanneshan ,&nbsp;Chae-Young Eun ,&nbsp;Xinyu Zhang ,&nbsp;Charlene DeKalb ,&nbsp;Bayan Mahgoub ,&nbsp;Hanaa Knaneh-Monem ,&nbsp;Sana Shah ,&nbsp;Alireza Sohrabi ,&nbsp;Stephanie K. Seidlits ,&nbsp;Reginald Hill","doi":"10.1016/j.mbplus.2022.100111","DOIUrl":"10.1016/j.mbplus.2022.100111","url":null,"abstract":"<div><p>In pancreatic ductal adenocarcinoma (PDAC), the abundant stromal cells which comprise the tumor microenvironment constitute more than 90% of the primary tumor bulk. Moreover, this desmoplastic environment has been found to be three times stiffer than normal pancreas tissue. Despite the importance of studying the desmoplastic environment of PDAC, there is still a lack of models designed to adequately recapitulate this complex stiff microenvironment, a critical hallmark of the disease that has been shown to induce chemoresistance. Here, we present a bio-mimetic, 3-dimensional co-culture system that integrates tumor organoids and host-matching stromal cancer associated-fibroblasts (CAFs) that recapitulates the complex, fibrotic matrix of PDAC using advanced biomaterials. With this model, we show that matrix-activated CAFs are able to “re-engineer” the fibrotic environment into a significantly stiffer environment through lysyl-oxidase dependent crosslinking. Moreover, we show that culture of CAFs in this model leads to an increase of exosomes; extracellular vesicles known to promote chemoresistance. Finally, using previously identified exosome inhibitors, climbazole and imipramine, we demonstrate how abrogation of exosome hypersecretion can reduce matrix stiffness-induced chemoresistance. These data highlight the importance of the development of new models that recapitulate not only the cellular composition found in PDAC tumors, but also the biophysical stresses, like stiffness, that the cells are exposed to in order to identify therapies that can overcome this critical feature which can contribute to the chemoresistance observed in patients. We believe that the 3D bio-mimetic model we have developed will be a valuable tool for the development, testing, and optimization of “mechano-medicines” designed to target the biophysical forces that lead to tumor growth and chemoresistance.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000114/pdfft?md5=2f4693aea30f614fc02bf017ef857fa5&pid=1-s2.0-S2590028522000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49610159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling the mechanical stiffness of pancreatic ductal adenocarcinoma","authors":"Delanyo Kpeglo ,&nbsp;Matthew D.G. Hughes ,&nbsp;Lorna Dougan ,&nbsp;Malcolm Haddrick ,&nbsp;Margaret A. Knowles ,&nbsp;Stephen D. Evans ,&nbsp;Sally A. Peyman","doi":"10.1016/j.mbplus.2022.100109","DOIUrl":"10.1016/j.mbplus.2022.100109","url":null,"abstract":"<div><p>Despite improvements in the understanding of disease biology, pancreatic ductal adenocarcinoma (PDAC) remains the most malignant cancer of the pancreas. PDAC constitutes ∼95% of all pancreatic cancers, and it is highly resistant to therapeutics. The increased tissue rigidity, which stems from the rich fibrotic stroma in the tumor microenvironment, is central to disease development, physiology, and resistance to drug perfusion. Pancreatic stellate cells (PSCs) are responsible for overproduction of extracellular matrix in the fibrotic stroma, and this is exacerbated by the overexpression of transforming growth factor-β (TGF-β). However, there are few <em>in vitro</em> PDAC models, which include both PSCs and TGF-β or mimic <em>in vivo</em>-like tumor stiffness. In this study, we present a three-dimensional <em>in vitro</em> PDAC model, which includes PSCs and TGF-β, and recapitulates PDAC tissue mechanical stiffness. Using oscillatory shear rheology, we show the mechanical stiffness of the model is within range of the PDAC tissue stiffness by day 21 of culture and highlight that the matrix environment is essential to adequately capture PDAC disease. PDAC is a complex, aggressive disease with poor prognosis, and biophysically relevant <em>in vitro</em> PDAC models, which take into account tissue mechanics, will provide improved tumor models for effective therapeutic assessment.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000096/pdfft?md5=d298c278086c2d17424b5fb7d6b56849&pid=1-s2.0-S2590028522000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48312705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenascin-C is a driver of inflammation in the DSS model of colitis","authors":"James Ozanne ,&nbsp;Brandon Shek ,&nbsp;Louise A. Stephen ,&nbsp;Amanda Novak ,&nbsp;Elspeth Milne ,&nbsp;Gerry Mclachlan ,&nbsp;Kim S. Midwood ,&nbsp;Colin Farquharson","doi":"10.1016/j.mbplus.2022.100112","DOIUrl":"10.1016/j.mbplus.2022.100112","url":null,"abstract":"<div><p>Inflammatory Bowel Disease (IBD) is a grouping of chronic inflammatory disorders of the gut. Tenascin-C is a pro-inflammatory, extracellular matrix protein found upregulated in IBD patients and whilst a pathological driver of chronic inflammation, its precise role in the etiology of IBD is unknown. To study tenascin-C’s role in colitis pathology we investigated its expression in a murine model of IBD. Wild-type (WT) or tenascin-C knockout (KO) male mice were left untreated or treated with dextran sodium sulphate (DSS) in their drinking water. Tenascin-C was upregulated at the mRNA level in the colitic distal colon of day eight DSS treated mice, coinciding with significant increases in gross and histological pathology. Immunohistochemistry localized this increase in tenascin-C to areas of inflammation and ulceration in the mucosa. Tenascin-C KO mice exhibited reduced gross pathology in comparison. These differences also extended to the histopathological level where reduced colonic inflammation and tissue damage were found in KO compared to WT mice. Furthermore, the severity of the distal colon lesions were less in the KO mice after 17 days of recovery from DSS treatment. This study demonstrates a role for tenascin-C as a driver of inflammatory pathology in a murine model of IBD and thus suggests neutralizing its pro-inflammatory activity could be explored as a therapeutic strategy for treating IBD.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000126/pdfft?md5=c84fa2713ddbfbe59b95991bc3be48ca&pid=1-s2.0-S2590028522000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42983271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell adhesivity distribution of glycocalyx digested cancer cells from high spatial resolution label-free biosensor measurements","authors":"N. Kanyo ,&nbsp;K.D. Kovács ,&nbsp;S.V. Kovács ,&nbsp;B. Béres ,&nbsp;B. Peter ,&nbsp;I. Székács ,&nbsp;R. Horvath","doi":"10.1016/j.mbplus.2022.100103","DOIUrl":"10.1016/j.mbplus.2022.100103","url":null,"abstract":"<div><p>The glycocalyx is a cell surface sugar layer of most cell types that greatly influences the interaction of cells with their environment. Its components are glycolipids, glycoproteins, and oligosaccharides. Interestingly, cancer cells have a thicker glycocalyx layer compared to healthy cells, but to date, there has been no consensus in the literature on the exact role of cell surface polysaccharides and their derivatives in cellular adhesion and signaling. In our previous work we discovered that specific glycocalyx components of cancer cells regulate the kinetics and strength of adhesion on RGD (arginine-glycine-aspartic acid) peptide-coated surfaces [1]. Depending on the employed enzyme concentration digesting specific components both adhesion strengthening and weakening could be observed by monitoring the averaged behavior of thousands of cells. The enzyme chondroitinase ABC (ChrABC) was used to digest the chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate components in the glycocalyx of cancer cells. In the present work, a high spatial resolution label-free optical biosensor was employed to monitor the adhesivity of cancer cells both at the single-cell and population level. Population-level distributions of single-cell adhesivity were first recorded and analyzed when ChrABC was added to the adhering cells. At relatively low and high ChrABC concentrations subpopulations with remarkably large and weak adhesivity were identified. The changes in the adhesivity distribution due to the enzyme treatment were analyzed and the subpopulations most affected by the enzyme treatment were highlighted. The presented results open up new directions in glycocalyx related cell adhesion research and in the development of more meaningful targeted cancer treatments affecting adhesion.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"14 ","pages":"Article 100103"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028522000035/pdfft?md5=7fbc8369a2f04689ff73cfc89a85b65f&pid=1-s2.0-S2590028522000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43045326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparanase as active player in endothelial glycocalyx remodeling","authors":"Valentina Masola ,&nbsp;Nicola Greco ,&nbsp;Giovanni Gambaro ,&nbsp;Marco Franchi ,&nbsp;Maurizio Onisto","doi":"10.1016/j.mbplus.2021.100097","DOIUrl":"10.1016/j.mbplus.2021.100097","url":null,"abstract":"<div><p>The surface of all animal cells is coated with a layer of carbohydrates linked in various ways to the outer side of the plasma membrane. These carbohydrates are mainly bound to proteins in the form of glycoproteins and proteoglycans and together with the glycolipids constitute the so-called glycocalyx. In particular, the endothelial glycocalyx that covers the luminal layer of the endothelium is composed of glycosaminoglycans (heparan sulphate -HS and hyaluronic acid -HA), proteoglycans (syndecans and glypicans) and adsorbed plasma proteins. Thanks to its ability to absorb water, this structure contributes to making the surface of the vessels slippery but at the same time acts by modulating the mechano-transduction of the vessels, the vascular permeability and the adhesion of leukocytes in thus regulating several physiological and pathological events. Among the various enzymes involved in the degradation of the glycocalyx, heparanase (HPSE) has been shown to be particularly involved. This enzyme is responsible for the cutting of heparan sulfate (HS) chains at the level of the proteoglycans of the endothelial glycocalyx whose dysfunction appears to have a role in organ fibrosis, sepsis and viral infection.</p><p>In this mini-review, we describe the mechanisms by which HPSE contributes to glycocalyx remodeling and then examine the role of glycocalyx degradation in the development of pathological conditions and pharmacological strategies to preserve glycocalyx during disease pathogenesis.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"13 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/1c/main.PMC8749438.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39688129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}