Matrix Biology Plus最新文献

{"title":"Spatial gene expression in the adult rat patellar tendon","authors":"Danielle Steffen ,&nbsp;Michael Mienaltowski ,&nbsp;Keith Baar","doi":"10.1016/j.mbplus.2023.100138","DOIUrl":"https://doi.org/10.1016/j.mbplus.2023.100138","url":null,"abstract":"<div><p>Tendons are dense connective tissues with relatively few cells which makes studying the molecular profile of the tissue challenging. There is not a consensus on the spatial location of various cell types within a tendon, nor the accompanying transcriptional profile. In the present study, we used two male rat patellar tendon samples for sequencing-based spatial transcriptomics to determine the gene expression profile. We integrated our data with a mouse Achilles single cell dataset to predict the cell type composition of the patellar tendon as a function of location within the tissue. The spatial location of the predicated cell types suggested that there were two populations of tendon fibroblasts, one located in the tendon midsubstance, while the other localized with red blood cells, pericytes, and immune cells to the tendon peripheral connective tissue. Of the highest expressed spatially variable genes, there were multiple genes with known function in tendon: Col1a1, Col1a2, Dcn, Fmod, Sparc, and Comp. Further, a novel spatially regulated gene (AABR07000398.1) with no known function was identified. The spatial gene expression of tendon associated genes (Scx, Thbs4, Tnmd, Can, Bgn, Lum, Adamts2, Lox, Ppib, Col2a1, Col3a1, Col6a2) was also visualized. Both patellar tendon samples had similar expression patterns for all these genes. This dataset provides new spatial insights into gene expression in a healthy tendon.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"19 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259002852300011X/pdfft?md5=92f789b40475e66f6e1aa25a6e729868&pid=1-s2.0-S259002852300011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138475136","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":"Temporal expression and spatial distribution of the proteoglycan versican during cardiac fibrosis development","authors":"Athiramol Sasi ,&nbsp;Andreas Romaine ,&nbsp;Pugazendhi Murugan Erusappan ,&nbsp;Arne Olav Melleby ,&nbsp;Almira Hasic ,&nbsp;Christen Peder Dahl ,&nbsp;Kaspar Broch ,&nbsp;Vibeke Marie Almaas ,&nbsp;Rosa Doñate Puertas ,&nbsp;H. Llewelyn Roderick ,&nbsp;Ida Gjervold Lunde ,&nbsp;Ivar Sjaastad ,&nbsp;Maria Vistnes ,&nbsp;Geir Christensen","doi":"10.1016/j.mbplus.2023.100135","DOIUrl":"10.1016/j.mbplus.2023.100135","url":null,"abstract":"<div><p>Cardiac fibrosis is a central pathological feature in several cardiac diseases, but the underlying molecular players are insufficiently understood. The extracellular matrix proteoglycan versican is elevated in heart failure and suggested to be a target for treatment. However, the temporal expression and spatial distribution of versican and the versican cleavage fragment containing the neoepitope DPEAAE in cardiac fibrosis remains to be elucidated. In this study, we have examined versican during cardiac fibrosis development in a murine pressure overload model and in patients with cardiomyopathies. We found that versican, mainly the V1 isoform, was expressed immediately after induction of pressure overload, preceding collagen accumulation, and versican protein levels extended from the perivascular region into the cardiac interstitium. In addition, we found increased production of versican by collagen expressing fibroblasts, and that it was deposited extensively in the fibrotic extracellular matrix during pressure overload. In cardiac cell cultures, the expression of versican was induced by the pro-fibrotic transforming growth factor beta and mechanical stretch. Furthermore, we observed that the proteolytic cleavage of versican (DPEAAE fragment) increased in the late phase of fibrosis development during pressure overload. In patients with hypertrophic and dilated cardiomyopathies, we found elevated levels of versican and a positive correlation between versican and collagen mRNA in the heart, as well as increased cleavage of full-length protein. Taken together, the temporal expression profile and the spatial distribution of both the full-length versican and the DPEAAE fragment observed in this study indicates a role for versican in development of cardiac fibrosis.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"19 ","pages":"Article 100135"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259002852300008X/pdfft?md5=2f40143c76be0e607a9220491b8dfec2&pid=1-s2.0-S259002852300008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135566416","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":"Visualization of basement membranes by a nidogen-based fluorescent reporter in mice","authors":"Sugiko Futaki ,&nbsp;Ayano Horimoto ,&nbsp;Chisei Shimono ,&nbsp;Naoko Norioka ,&nbsp;Yukimasa Taniguchi ,&nbsp;Hitomi Hamaoka ,&nbsp;Mari Kaneko ,&nbsp;Mayo Shigeta ,&nbsp;Takaya Abe ,&nbsp;Kiyotoshi Sekiguchi ,&nbsp;Yoichi Kondo","doi":"10.1016/j.mbplus.2023.100133","DOIUrl":"10.1016/j.mbplus.2023.100133","url":null,"abstract":"<div><p>Basement membranes (BMs) are thin, sheet-like extracellular structures that cover the basal side of epithelial and endothelial tissues and provide structural and functional support to adjacent cell layers. The molecular structure of BMs is a fine meshwork that incorporates specialized extracellular matrix proteins. Recently, live visualization of BMs in invertebrates demonstrated that their structure is flexible and dynamically rearranged during cell differentiation and organogenesis. However, the BM dynamics in mammalian tissues remain to be elucidated. We developed a mammalian BM imaging probe based on nidogen-1, a major BM-specific protein. Recombinant human nidogen-1 fused with an enhanced green fluorescent protein (Nid1-EGFP) retains its ability to bind to other BM proteins, such as laminin, type IV collagen, and perlecan, in a solid-phase binding assay. When added to the culture medium of embryoid bodies derived from mouse ES cells, recombinant Nid1-EGFP accumulated in the BM zone of embryoid bodies, and BMs were visualized <em>in vitro</em>. For <em>in vivo</em> BM imaging, a knock-in reporter mouse line expressing human nidogen-1 fused to the red fluorescent protein mCherry (R26-CAG-Nid1-mCherry) was generated. R26-CAG-Nid1-mCherry showed fluorescently labeled BMs in early embryos and adult tissues, such as the epidermis, intestine, and skeletal muscles, whereas BM fluorescence was unclear in several other tissues, such as the lung and heart. In the retina, Nid1-mCherry fluorescence visualized the BMs of vascular endothelium and pericytes. In the developing retina, Nid1-mCherry fluorescence labeled the BM of the major central vessels; however, the BM fluorescence were hardly observed in the peripheral growing tips of the vascular network, despite the presence of endothelial BM. Time-lapse observation of the retinal vascular BM after photobleaching revealed gradual recovery of Nid1-mCherry fluorescence, suggesting the turnover of BM components in developing retinal blood vessels. To the best of our knowledge, this is the first demonstration of <em>in vivo</em> BM imaging using a genetically engineered mammalian model. Although R26-CAG-Nid1-mCherry has some limitations as an <em>in vivo</em> BM imaging model, it has potential applications in the study of BM dynamics during mammalian embryogenesis, tissue regeneration, and pathogenesis.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"18 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773433","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":"Whole organism profiling of the Timp gene family","authors":"David Peeney ,&nbsp;Yu Fan ,&nbsp;Sadeechya Gurung ,&nbsp;Carolyn Lazaroff ,&nbsp;Shashikala Ratnayake ,&nbsp;Andrew Warner ,&nbsp;Baktiar Karim ,&nbsp;Daoud Meerzaman ,&nbsp;William G. Stetler-Stevenson","doi":"10.1016/j.mbplus.2023.100132","DOIUrl":"10.1016/j.mbplus.2023.100132","url":null,"abstract":"<div><p>Tissue inhibitor of metalloproteinases (TIMPs/Timps) are an endogenous family of widely expressed matrisome-associated proteins that were initially identified as inhibitors of matrix metalloproteinase activity (Metzincin family proteases). Consequently, TIMPs are often considered simply as protease inhibitors by many investigators. However, an evolving list of new metalloproteinase-independent functions for TIMP family members suggests that this concept is outdated. These novel TIMP functions include direct agonism/antagonism of multiple transmembrane receptors, as well as functional interactions with matrisome targets. While the family was fully identified over two decades ago, there has yet to be an in-depth study describing the expression of TIMPs in normal tissues of adult mammals. An understanding of the tissues and cell-types that express TIMPs 1 through 4, in both normal and disease states are important to contextualize the growing functional capabilities of TIMP proteins, which are often dismissed as non-canonical. Using publicly available single cell RNA sequencing data from the Tabula Muris Consortium, we analyzed approximately 100,000 murine cells across eighteen tissues from non-diseased organs, representing seventy-three annotated cell types, to define the diversity in Timp gene expression across healthy tissues. We describe the unique expression profiles across tissues and organ-specific cell types that all four Timp genes display. Within annotated cell-types, we identify clear and discrete cluster-specific patterns of Timp expression, particularly in cells of stromal and endothelial origins. RNA in-situ hybridization across four organs expands on the scRNA sequencing analysis, revealing novel compartments associated with individual Timp expression. These analyses emphasize a need for specific studies investigating the functional significance of Timp expression in the identified tissues and cell sub-types. This understanding of the tissues, specific cell types and microenvironment conditions in which Timp genes are expressed adds important physiological context to the growing array of novel functions for TIMP proteins.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"18 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121480/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743704","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 collagen fibrils isolated from high stress and low stress tendons show differing susceptibility to enzymatic degradation by the interstitial collagenase matrix metalloproteinase-1 (MMP-1)","authors":"Kelsey Y. Gsell ,&nbsp;Samuel P. Veres ,&nbsp;Laurent Kreplak","doi":"10.1016/j.mbplus.2023.100129","DOIUrl":"10.1016/j.mbplus.2023.100129","url":null,"abstract":"<div><p>Bovine forelimb flexor and extensor tendons serve as a model for examining high stress, energy storing and low stress, positional tendons, respectively. Previous research has shown structural differences between the collagen fibrils of these tissues. The nanoscale collagen fibrils of flexor tendons are smaller in size, more heavily crosslinked, and respond differently to mechanical loading. Meanwhile, energy storing tendons undergo less collagen turnover compared to positional tendons and are more commonly injured. These observations raise the question of whether collagen fibril structure influences the collagen degradation processes necessary for remodelling. Atomic force microscopy was used to image dry collagen fibrils before and after 5-hour exposure to matrix metalloproteinase-1 (MMP-1) to detect changes in fibril size. Collagen fibrils from three tissue types were studied: bovine superficial digital flexor tendons, matched-pair bovine lateral digital extensor tendons, and rat tail tendons. Compared to control fibrils exposed only to buffer, a significant decrease in fibril cross-sectional area (CSA) following MMP-1 exposure was observed for bovine extensor and rat tail fibrils, with larger fibrils experiencing a greater magnitude of CSA decrease in both fibril types. Fibrils from bovine flexor tendons, on the other hand, showed no decrease in CSA when exposed to MMP-1. The result did not appear to be linked to the small size of flexor fibrils, as equivalently sized extensor fibrils were readily degraded by the enzyme. Increased proteolytic resistance of collagen fibrils from high stress tendons may help to explain the longevity of collagen within these tissues <em>in vivo</em>.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"18 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465323","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 extracellular matrix of dystrophic mouse diaphragm accounts for the majority of its passive stiffness and is resistant to collagenase digestion","authors":"Ross P. Wohlgemuth ,&nbsp;Ryan M. Feitzinger ,&nbsp;Kyle E. Henricson ,&nbsp;Daryl T. Dinh ,&nbsp;Sarah E. Brashear ,&nbsp;Lucas R. Smith","doi":"10.1016/j.mbplus.2023.100131","DOIUrl":"10.1016/j.mbplus.2023.100131","url":null,"abstract":"<div><p>The healthy skeletal muscle extracellular matrix (ECM) has several functions including providing structural integrity to myofibers, enabling lateral force transmission, and contributing to overall passive mechanical properties. In diseases such as Duchenne Muscular dystrophy, there is accumulation of ECM materials, primarily collagen, which results in fibrosis. Previous studies have shown that fibrotic muscle is often stiffer than healthy muscle, in part due to the increased number and altered architecture of collagen fibers within the ECM. This would imply that the fibrotic matrix is stiffer than the healthy matrix. However, while previous studies have attempted to quantify the extracellular contribution to passive stiffness in muscle, the outcomes are dependent on the type of method used. Thus, the goals of this study were to compare the stiffness of healthy and fibrotic muscle ECM and to demonstrate the efficacy of two methods for quantifying extracellular-based stiffness in muscle, namely decellularization and collagenase digestion. These methods have been demonstrated to remove the muscle fibers or ablate collagen fiber integrity, respectively, while maintaining the contents of the extracellular matrix. Using these methods in conjunction with mechanical testing on wildtype and D2.<em>mdx</em> mice, we found that a majority of passive stiffness in the diaphragm is dependent on the ECM, and the D2.<em>mdx</em> diaphragm ECM is resistant to digestion by bacterial collagenase. We propose that this resistance is due to the increased collagen cross-links and collagen packing density in the ECM of the D2.<em>mdx</em> diaphragm. Taken altogether, while we did not find increased stiffness of the fibrotic ECM, we did observe that the D2.<em>mdx</em> diaphragm conveyed resistance against collagenase digestion. These findings demonstrate how different methods for measuring ECM-based stiffness each have their own limitations and can produce different results.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"18 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/47/main.PMC10036937.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9198921","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":"Presence of type IIB procollagen in mouse articular cartilage and growth plate is revealed by immuno-histochemical analysis with a novel specific antibody","authors":"Emeline Perrier-Groult,&nbsp;Shérine Moustaghfir,&nbsp;Marielle Pasdeloup,&nbsp;Jean-Daniel Malcor,&nbsp;Jérôme Lafont,&nbsp;Frédéric Mallein-Gerin","doi":"10.1016/j.mbplus.2023.100130","DOIUrl":"10.1016/j.mbplus.2023.100130","url":null,"abstract":"<div><p>Type II collagen is the major fibrillar collagen in cartilage. It is synthesized in the form of precursors (procollagens) containing N- and C-terminal propeptides. The two main isoforms of type II procollagen protein are type IIA and type IIB procollagens, generated in a developmentally regulated manner by differential splicing of the primary gene transcript. Isoform IIA contains exon 2 and is produced mainly by chondroprogenitor cells while isoform IIB lacks exon 2 and is produced by differentiated chondrocytes. Thus, expression of IIA and IIB isoforms are reliable markers for identifying the differentiation status of chondrocytes but their biological function in the context of skeletal development is still not yet fully understood. Specific antibodies against IIA and IIB procollagen isoforms are already available. In this study, a synthetic peptide spanning the junction between exon 1 and exon 3 of the murine sequence was used as an immunogen to generate a novel rabbit polyclonal antibody directed against procollagen IIB. Characterization of this antibody by Western-blotting analysis of murine cartilage extracts and ELISA tests demonstrated its specificity to the type IIB isoform. Furthermore, by immunohistochemical studies, this antibody allowed the detection of procollagen IIB in embryonic cartilage as well as in articular cartilage and growth plate of young adult mice. Interestingly, this is the first antibody that has allowed the detection of procollagen IIB at both the intra- and extracellular level. This antibody therefore represents an interesting new tool for monitoring the spatial and temporal distribution of IIB isoforms in skeletal tissues of mouse models and for tracking the trafficking and processing of type IIB procollagen.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"18 ","pages":"Article 100130"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/10/main.PMC10024168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9153829","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 glycocalyx: Pathobiology and repair","authors":"Jillian R. Richter ,&nbsp;Ralph D. Sanderson","doi":"10.1016/j.mbplus.2023.100128","DOIUrl":"10.1016/j.mbplus.2023.100128","url":null,"abstract":"","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"17 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f6/fa/main.PMC9923180.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871691","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":"Fibrosis resolution in the mouse liver: Role of Mmp12 and potential role of calpain 1/2","authors":"Toshifumi Sato ,&nbsp;Kimberly Z. Head ,&nbsp;Jiang Li ,&nbsp;Christine E. Dolin ,&nbsp;Daniel Wilkey ,&nbsp;Nolan Skirtich ,&nbsp;Katelyn Smith ,&nbsp;Dylan D. McCreary ,&nbsp;Sylvia Liu ,&nbsp;Juliane I. Beier ,&nbsp;Aatur D. Singhi ,&nbsp;Ryan M. McEnaney ,&nbsp;Michael L. Merchant ,&nbsp;Gavin E. Arteel","doi":"10.1016/j.mbplus.2022.100127","DOIUrl":"10.1016/j.mbplus.2022.100127","url":null,"abstract":"<div><p>Although most work has focused on resolution of collagen ECM, fibrosis resolution involves changes to several ECM proteins. The purpose of the current study was twofold: 1) to examine the role of MMP12 and elastin; and 2) to investigate the changes in degraded proteins in plasma (i.e., the “degradome”) in a preclinical model of fibrosis resolution. Fibrosis was induced by 4 weeks carbon tetrachloride (CCl₄) exposure, and recovery was monitored for an additional 4 weeks. Some mice were treated with daily MMP12 inhibitor (MMP408) during the resolution phase. Liver injury and fibrosis was monitored by clinical chemistry, histology and gene expression. The release of degraded ECM peptides in the plasma was analyzed using by 1D-LC-MS/MS, coupled with PEAKS Studio (v10) peptide identification. Hepatic fibrosis and liver injury rapidly resolved in this mouse model. However, some collagen fibrils were still present 28d after cessation of CCl₄. Despite this persistent collagen presence, expression of canonical markers of fibrosis were also normalized. The inhibition of MMP12 dramatically delayed fibrosis resolution under these conditions. LC-MS/MS analysis identified that several proteins were being degraded even at late stages of fibrosis resolution. Calpains 1/2 were identified as potential new proteases involved in fibrosis resolution. CONCLUSION. The results of this study indicate that remodeling of the liver during recovery from fibrosis is a complex and highly coordinated process that extends well beyond the degradation of the collagenous scar. These results also indicate that analysis of the plasma degradome may yield new insight into the mechanisms of fibrosis recovery, and by extension, new “theragnostic” targets. Lastly, a novel potential role for calpain activation in the degradation and turnover of proteins was identified.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"17 ","pages":"Article 100127"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cf/aa/main.PMC9826883.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796941","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":"Small molecule inhibitors of mammalian glycosylation","authors":"Karim Almahayni ,&nbsp;Malte Spiekermann ,&nbsp;Antonio Fiore ,&nbsp;Guoqiang Yu ,&nbsp;Kayvon Pedram ,&nbsp;Leonhard Möckl","doi":"10.1016/j.mbplus.2022.100108","DOIUrl":"10.1016/j.mbplus.2022.100108","url":null,"abstract":"<div><p>Glycans are one of the fundamental biopolymers encountered in living systems. Compared to polynucleotide and polypeptide biosynthesis, polysaccharide biosynthesis is a uniquely combinatorial process to which interdependent enzymes with seemingly broad specificities contribute. The resulting intracellular cell surface, and secreted glycans play key roles in health and disease, from embryogenesis to cancer progression. The study and modulation of glycans in cell and organismal biology is aided by small molecule inhibitors of the enzymes involved in glycan biosynthesis. In this review, we survey the arsenal of currently available inhibitors, focusing on agents which have been independently validated in diverse systems. We highlight the utility of these inhibitors and drawbacks to their use, emphasizing the need for innovation for basic research as well as for therapeutic applications.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"16 ","pages":"Article 100108"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/f7/main.PMC9713294.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10536198","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}