Matrix Biology Plus最新文献

{"title":"Uncovering mediators of collagen degradation in the tumor microenvironment","authors":"Marie-Louise Thorseth ,&nbsp;Marco Carretta ,&nbsp;Christina Jensen ,&nbsp;Kasper Mølgaard ,&nbsp;Henrik J. Jürgensen ,&nbsp;Lars H. Engelholm ,&nbsp;Niels Behrendt ,&nbsp;Nicholas Willumsen ,&nbsp;Daniel H. Madsen","doi":"10.1016/j.mbplus.2022.100101","DOIUrl":"10.1016/j.mbplus.2022.100101","url":null,"abstract":"<div><p>Increased remodeling of the extracellular matrix in malignant tumors has been shown to correlate with tumor aggressiveness and a poor prognosis. This remodeling involves degradation of the original extracellular matrix (ECM) and deposition of a new tumor-supporting ECM. The main constituent of the ECM is collagen and collagen turnover mainly occurs in a sequential manner, where initial proteolytic cleavage of the insoluble fibers is followed by cellular internalization of large well-defined collagen fragments for lysosomal degradation. However, despite extensive research in the field, a lack of consensus on which cell types within the tumor microenvironment express the involved proteases still exists. Furthermore, the relative contribution of different cell types to collagen internalization is not well-established. Here, we developed quantitative <em>ex vivo</em> collagen degradation assays and show that the proteases responsible for the initial collagen cleavage in two murine syngeneic tumor models are matrix metalloproteinases produced by cancer-associated fibroblasts and that collagen degradation fragments are endocytosed primarily by tumor-associated macrophages and cancer-associated fibroblasts from the tumor stroma. Using tumors from mannose receptor-deficient mice, we show that this receptor is essential for collagen-internalization by tumor-associated macrophages. Together, these findings identify the cell types responsible for the entire collagen degradation pathway, from initial cleavage to endocytosis of fragments for intracellular degradation.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"13 ","pages":"Article 100101"},"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/5d/5e/main.PMC8841889.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948820","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":"PRIMUS: Comprehensive proteomics of mouse intervertebral discs that inform novel biology and relevance to human disease modelling","authors":"Mateusz Kudelko ,&nbsp;Peikai Chen ,&nbsp;Vivian Tam ,&nbsp;Ying Zhang ,&nbsp;Oi-Yin Kong ,&nbsp;Rakesh Sharma ,&nbsp;Tiffany Y.K. Au ,&nbsp;Michael Kai-Tsun To ,&nbsp;Kathryn S.E. Cheah ,&nbsp;Wilson C.W. Chan ,&nbsp;Danny Chan","doi":"10.1016/j.mbplus.2021.100082","DOIUrl":"10.1016/j.mbplus.2021.100082","url":null,"abstract":"<div><p>Mice are commonly used to study intervertebral disc (IVD) biology and related diseases such as IVD degeneration. Discs from both the lumbar and tail regions are used. However, little is known about compartmental characteristics in the different regions, nor their relevance to the human setting, where a functional IVD unit depends on a homeostatic proteome. Here, we address these major gaps through comprehensive proteomic profiling and in-depth analyses of 8-week-old healthy murine discs, followed by comparisons with human. Leveraging on a dataset of over 2,700 proteins from 31 proteomic profiles, we identified key molecular and cellular differences between disc compartments and spine levels, but not gender. The nucleus pulposus (NP) and annulus fibrosus (AF) compartments differ the most, both in matrisome and cellularity contents. Differences in the matrisome are consistent with the fibrous nature required for tensile strength in the AF and hydration property in the NP. Novel findings for the NP cells included an enrichment in cell junction proteins for cell–cell communication (Cdh2, Dsp and Gja1) and osmoregulation (Slc12a2 and Wnk1). In NP cells, we detected heterogeneity of vacuolar organelles; where about half have potential lysosomal function (Vamp3, Copb2, Lamp1/2, Lamtor1), some contain lipid droplets and others with undefined contents. The AF is enriched in proteins for the oxidative stress responses (Sod3 and Clu). Interestingly, mitochondrial proteins are elevated in the lumbar than tail IVDs that may reflect differences in metabolic requirement. Relative to the human, cellular and structural information are conserved for the AF. Even though the NP is more divergent between mouse and human, there are similarities at the level of cell biology. Further, common cross-species markers were identified for both NP (KRT8/19, CD109) and AF (COL12A1). Overall, mouse is a relevant model to study IVD biology, and an understanding of the limitation will facilitate research planning and data interpretation, maximizing the translation of research findings to human IVDs.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39324449","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":"Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans","authors":"Frank Gondelaud ,&nbsp;Mathilde Bouakil ,&nbsp;Aurélien Le Fèvre ,&nbsp;Adriana Erica Miele ,&nbsp;Fabien Chirot ,&nbsp;Bertrand Duclos ,&nbsp;Adam Liwo ,&nbsp;Sylvie Ricard-Blum","doi":"10.1016/j.mbplus.2021.100081","DOIUrl":"10.1016/j.mbplus.2021.100081","url":null,"abstract":"<div><p>Syndecans are membrane proteoglycans regulating extracellular matrix assembly, cell adhesion and signaling. Their ectodomains can be shed from the cell surface, and act as paracrine and autocrine effectors or as competitors of full-length syndecans. We report the first biophysical characterization of the recombinant ectodomains of the four human syndecans using biophysical techniques, and show that they behave like flexible random-coil intrinsically disordered proteins, and adopt several conformation ensembles in solution. We have characterized their conformational landscapes using native mass spectrometry (MS) and ion-mobility MS, and demonstrated that the syndecan ectodomains explore the majority of their conformational landscape, from minor compact, globular-like, conformations to extended ones. We also report that the ectodomain of syndecan-4, corresponding to a natural isoform, is able to dimerize via a disulfide bond. We have generated a three-dimensional model of the C-terminus of this dimer, which supports the dimerization via a disulfide bond. Furthermore, we have mapped the NXIP adhesion motif of syndecans and their sequences involved in the formation of ternary complexes with integrins and growth factor receptors on the major conformations of their ectodomains, and shown that these sequences are not accessible in all the conformations, suggesting that only some of them are biologically active. Lastly, although the syndecan ectodomains have a far lower number of amino acid residues than their membrane partners, their intrinsic disorder and flexibility allow them to adopt extended conformations, which have roughly the same size as the cell surface receptors (e.g., integrins and growth factor receptors) they bind to.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39402756","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":"Collagen fibril assembly: New approaches to unanswered questions","authors":"Christopher K. Revell ,&nbsp;Oliver E. Jensen ,&nbsp;Tom Shearer ,&nbsp;Yinhui Lu ,&nbsp;David F. Holmes ,&nbsp;Karl E. Kadler","doi":"10.1016/j.mbplus.2021.100079","DOIUrl":"10.1016/j.mbplus.2021.100079","url":null,"abstract":"<div><p>Collagen fibrils are essential for metazoan life. They are the largest, most abundant, and most versatile protein polymers in animals, where they occur in the extracellular matrix to form the structural basis of tissues and organs. Collagen fibrils were first observed at the turn of the 20th century. During the last 40 years, the genes that encode the family of collagens have been identified, the structure of the collagen triple helix has been solved, the many enzymes involved in the post-translational modifications of collagens have been identified, mutations in the genes encoding collagen and collagen-associated proteins have been linked to heritable disorders, and changes in collagen levels have been associated with a wide range of diseases, including cancer. Yet despite extensive research, a full understanding of how cells assemble collagen fibrils remains elusive. Here, we review current models of collagen fibril self-assembly, and how cells might exert control over the self-assembly process to define the number, length and organisation of fibrils in tissues.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39303382","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":"Runx2 is required for hypertrophic chondrocyte mediated degradation of cartilage matrix during endochondral ossification","authors":"Harunur Rashid,&nbsp;Haiyan Chen,&nbsp;Amjad Javed","doi":"10.1016/j.mbplus.2021.100088","DOIUrl":"10.1016/j.mbplus.2021.100088","url":null,"abstract":"<div><p>The RUNX2 transcription factor is a key regulator for the development of cartilage and bone. Global or resting chondrocyte-specific deletion of the <em>Runx2</em> gene results in failure of chondrocyte hypertrophy, endochondral ossification, and perinatal lethality. The terminally mature hypertrophic chondrocyte regulates critical steps of endochondral ossification. Importantly, expression of the <em>Runx2</em> gene starts in the resting chondrocyte and increases progressively, reaching the maximum level in hypertrophic chondrocytes. However, the RUNX2 role after chondrocyte hypertrophy remains unknown. To answer this question, we deleted the <em>Runx2</em> gene specifically in hypertrophic chondrocytes using the Col10-Cre line. Mice lacking the <em>Runx2</em> gene in hypertrophic chondrocytes (<em>Runx2^HC/HC</em>) survive but exhibit limb dwarfism. Interestingly, the length of the hypertrophic chondrocyte zone is doubled in the growth plate of <em>Runx2^HC/HC</em> mice. Expression of pro-apoptotic <em>Bax</em> decreased significantly while anti-apoptotic <em>Bcl2</em> remains unchanged leading to a four-fold increase in the <em>Bcl2</em>/<em>Bax</em> ratio in mutant mice. In line with this, a significant reduction in apoptosis of <em>Runx2^HC/HC</em> hypertrophic chondrocyte is noted. A large amount of cartilage matrix is present in the long bones that extend toward the diaphyseal region of <em>Runx2^HC/HC</em> mice. This is not due to enhanced synthesis of the cartilage matrix as the expression of both collagen type 2 and aggrecan were comparable among <em>Runx2^HC/HC</em> and WT littermates. Our qPCR analysis demonstrates the increased amount of cartilage matrix is due to impaired expression of cartilage degrading enzymes such as metalloproteinase and aggrecanase as well as tissue inhibitor of metalloproteinases. Moreover, a significant decrease of TRAP positive chondroclasts was noted along the cartilage islands in <em>Runx2^HC/HC</em> mice. Consistently, qPCR data showed an 81% reduction in the <em>Rankl</em>/<em>Opg</em> ratio in <em>Runx2^HC/HC</em> littermates, which is inhibitory for chondroclast differentiation. Finally, we assess if increase cartilage matrix in <em>Runx2^HC/HC</em> mice serves as a template for bone and mineral deposition using micro-CT and Von Kossa. The mutant mice exhibit a significant increase in trabecular bone mass compared to littermates. In summary, our findings have uncovered a novel role of Runx2 in apoptosis of hypertrophic chondrocytes and degradation of cartilage matrix during endochondral ossification.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/53/main.PMC8586806.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39644967","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":"Structural studies of elastic fibre and microfibrillar proteins","authors":"Mukti Singh,&nbsp;Mark Becker,&nbsp;Alan R.F. Godwin,&nbsp;Clair Baldock","doi":"10.1016/j.mbplus.2021.100078","DOIUrl":"10.1016/j.mbplus.2021.100078","url":null,"abstract":"<div><p>Elastic tissues owe their functional properties to the composition of their extracellular matrices, particularly the range of extracellular, multidomain extensible elastic fibre and microfibrillar proteins. These proteins include elastin, fibrillin, latent TGFβ binding proteins (LTBPs) and collagens, where their biophysical and biochemical properties not only give the matrix structural integrity, but also play a vital role in the mechanisms that underlie tissue homeostasis. Thus far structural information regarding the structure and hierarchical assembly of these molecules has been challenging and the resolution has been limited due to post-translational modification and their multidomain nature leading to flexibility, which together result in conformational and structural heterogeneity. In this review, we describe some of the matrix proteins found in elastic fibres and the new emerging techniques that can shed light on their structure and dynamic properties.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39281140","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":"Protection and rebuilding of the endothelial glycocalyx in sepsis – Science or fiction?","authors":"Carolin Christina Drost,&nbsp;Alexandros Rovas,&nbsp;Philipp Kümpers","doi":"10.1016/j.mbplus.2021.100091","DOIUrl":"10.1016/j.mbplus.2021.100091","url":null,"abstract":"<div><p>The endothelial glycocalyx (eGC), a delicate carbohydrate-rich structure lining the luminal surface of the vascular endothelium, is vital for maintenance of microvascular homeostasis. In sepsis, damage of the eGC triggers the development of vascular hyperpermeability with consecutive edema formation and organ failure. While there is evidence that protection or rebuilding of the eGC might counteract sepsis-induced vascular leakage and improve outcome, approved therapeutics are not yet available. This narrative review aims to outline possible therapeutic strategies to ameliorate organ dysfunction caused by eGC impairment.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/65/main.PMC8633034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790977","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":"Basement membranes in obstructive pulmonary diseases","authors":"Bart G.J. Dekkers ,&nbsp;Shehab I. Saad ,&nbsp;Leah J. van Spelde ,&nbsp;Janette K. Burgess","doi":"10.1016/j.mbplus.2021.100092","DOIUrl":"10.1016/j.mbplus.2021.100092","url":null,"abstract":"<div><p>Increased and changed deposition of extracellular matrix proteins is a key feature of airway wall remodeling in obstructive pulmonary diseases, including asthma and chronic obstructive pulmonary disease. Studies have highlighted that the deposition of various basement membrane proteins in the lung tissue is altered and that these changes reflect tissue compartment specificity. Inflammatory responses in both diseases may result in the deregulation of production and degradation of these proteins. In addition to their role in tissue development and integrity, emerging evidence indicates that basement membrane proteins also actively modulate cellular processes in obstructive airway diseases, contributing to disease development, progression and maintenance. In this review, we summarize the changes in basement membrane composition in airway remodeling in obstructive airway diseases and explore their potential application as innovative targets for treatment development.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100092"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790979","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 potential role of glycosaminoglycans in serum amyloid A fibril formation by in silico approaches","authors":"Martyna Maszota-Zieleniak,&nbsp;Annemarie Danielsson,&nbsp;Sergey A. Samsonov","doi":"10.1016/j.mbplus.2021.100080","DOIUrl":"https://doi.org/10.1016/j.mbplus.2021.100080","url":null,"abstract":"<div><p>Serum amyloid A (SAA) is actively involved in such pathological processes as atherosclerosis, rheumatoid arthritis, cancer and Alzheimer's disease by its aggregation. One of the factors that can attenuate its aggregation and so affects its physiological role is its interactions with glycosminoglycans (GAGs), linear anionic periodic polysaccharides. These molecules located in the extracellular matrix of the cell are highly variable in their chemical composition and sulfation patterns. Despite the available experimental evidence of SAA-GAG interactions, no mechanistic details at atomic level have been reported for these systems so far. In our work we aimed to apply diverse computational tools to characterize SAA-GAG complexes formation and to answer questions about their potential specificity, energetic patterns, particular SAA residues involved in these interactions, favourable oligomeric state of the protein and the potential influence of GAGs on SAA aggregation. Molecular docking, conventional and replica exchange molecular dynamics approaches were applied to corroborate the experimental knowledge and to propose the corresponding molecular models. SAA-GAG complex formation was found to be electrostatics-driven and rather unspecific of a GAG sulfation pattern, more favorable for the dimer than for the monomer when binding to a short GAG oligosaccharide through its N-terminal helix, potentially contributing to the unfolding of this helix, which could lead to the promotion of the protein aggregation. The data obtained add to the specific knowledge on SAA-GAG systems and deepen the general understanding of protein-GAG interactions that is of a considerable value for the development of GAG-based approaches in a broad theurapeutic context.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91590717","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":"Four decades in the making: Collagen III and mechanisms of vascular Ehlers Danlos Syndrome","authors":"Ramla Omar ,&nbsp;Fransiska Malfait ,&nbsp;Tom Van Agtmael","doi":"10.1016/j.mbplus.2021.100090","DOIUrl":"10.1016/j.mbplus.2021.100090","url":null,"abstract":"<div><p>Vascular Ehlers Danlos (vEDS) syndrome is a severe multi-systemic connective tissue disorder characterized by risk of dissection and rupture of the arteries, gastro-intestinal tract and gravid uterus. vEDS is caused by mutations in <em>COL3A1</em>, that encodes the alpha 1 chain of type III collagen, which is a major extracellular matrix component of the vasculature and hollow organs. The first causal mutations were identified in the 1980s but progress in our understanding of the pathomolecular mechanisms has been limited. Recently, the application of more refined animal models combined with global omics approaches has yielded important new insights both in terms of disease mechanisms and potential for therapeutic intervention. However, it is also becoming apparent that vEDS is a complex disorder in terms of its molecular disease mechanisms with a poorly understood allelic and mechanistic heterogeneity. In this brief review we will focus our attention on the disease mechanisms of <em>COL3A1</em> mutations and vEDS, and recent progress in therapeutic approaches using animal models.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39680100","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}