Matrix Biology最新文献

Oligomerisation of pentraxin-3: Insights from cryoEM 五胜肽-3的寡聚化：低温电子显微镜的启示。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-04-03 DOI: 10.1016/j.matbio.2025.04.001

Antonio Inforzato , Anthony J. Day

{"title":"Oligomerisation of pentraxin-3: Insights from cryoEM","authors":"Antonio Inforzato , Anthony J. Day","doi":"10.1016/j.matbio.2025.04.001","DOIUrl":"10.1016/j.matbio.2025.04.001","url":null,"abstract":"<div><div>Pentraxin-3 (PTX3) is a secreted protein with roles in the stabilisation of hyaluronan-rich extracellular matrices involved in reproductive biology and inflammatory processes, as well as additional functions in innate immunity and cancer. Our recent structural studies (Shah <em>et al.</em>, 2025; DOI:10.1016/j.matbio.2025.01.002), involving X-ray crystallography, cryo-electron microscopy (cryoEM) and AlphaFold modelling, have provided clues as to how PTX3 becomes assembled into an octamer from eight identical protomer subunits. Here it was proposed that four protomers initially form a tetramer, composed of a highly extended N-terminal region consisting of coiled-coil structures and C-terminal pentraxin domains, where two tetramers then immediately align and associate via an extensive network of salt bridges, allowing stabilisation of the octamer via the formation of disulphide bonds. However, a paper published around the same time provides an alternative perspective (Guo <em>et al</em>., 2025; DOI: 10.1016/j.ijbiomac.2024.139207). The authors propose, based on cryoEM analyses, that in addition to octamers, stable dimers, tetramers and hexamers of PTX3 can also assemble, where it is the dimers that provide the ‘building blocks’ for generation of the various oligomeric forms. In this commentary we suggest that the presence of dimers, tetramers and hexamers is likely an artefact of the construct used in recombinant expression, since the existence of these oligomers is not consistent with other studies on PTX3. We also provide a model to clarify how protomers become assembled into an octamer via sequential formation of a disulphide-linked tetramer, non-covalent association of two tetramers through aligned ionic interactions and the formation of disulphide bonds between the C-terminal pentraxin domains.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 22-26"},"PeriodicalIF":4.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toward a rational therapeutic for elastin related disease: Key considerations for elastin based regenerative medicine strategies

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-28 DOI: 10.1016/j.matbio.2025.03.003

Meysam Ganjibakhsh , Yanina Tkachenko , Russell H. Knutsen , Beth A. Kozel

{"title":"Toward a rational therapeutic for elastin related disease: Key considerations for elastin based regenerative medicine strategies","authors":"Meysam Ganjibakhsh , Yanina Tkachenko , Russell H. Knutsen , Beth A. Kozel","doi":"10.1016/j.matbio.2025.03.003","DOIUrl":"10.1016/j.matbio.2025.03.003","url":null,"abstract":"<div><div>Elastin is a connective tissue protein, produced from the <em>ELN</em> gene, that provides elasticity and recoil to tissues that stretch, such as the large arteries of the body, lung parenchyma, skin, ligaments and elastic cartilages. It is produced as a soluble monomer, tropoelastin, that when cross-linked in the extracellular space generates a polymer that is extraordinarily stable, with a predicted half-life of >70 years. Although data suggest ongoing elastin transcription, it is rare to see new elastin deposited outside of its tight developmental window. Consequently, elastin-related disease comes about primarily in one of three scenarios: (1) inadequate elastin deposition, (2) production of poor-quality elastic fibers, or (3) increased destruction of previously deposited elastin. By understanding the pathways controlling elastin production and maintenance, we can design new therapeutics to thwart those abnormal processes. In this review, we will summarize the diseases arising from genetic and environmental alteration of elastin (Williams syndrome, supravalvar aortic stenosis, autosomal dominant cutis laxa, and ELN-related vascular and connective tissue dysfunction) and then describe the mechanisms controlling elastin production and maintenance that might be manipulated to generate novel therapeutics aimed at these conditions. We will end by summarizing existing therapeutic strategies targeting these disease mechanisms before outlining future approaches that may better solve the challenges associated with elastin based regenerative medicine.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 8-21"},"PeriodicalIF":4.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights on perlecan and Schwartz–Jampel syndrome 关于perlecan和Schwartz-Jampel综合征的结构见解。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-19 DOI: 10.1016/j.matbio.2025.03.002

Anil A. Sohail , M. Kristian Koski , Lloyd W. Ruddock

{"title":"Structural insights on perlecan and Schwartz–Jampel syndrome","authors":"Anil A. Sohail , M. Kristian Koski , Lloyd W. Ruddock","doi":"10.1016/j.matbio.2025.03.002","DOIUrl":"10.1016/j.matbio.2025.03.002","url":null,"abstract":"<div><div>Perlecan is an essential multi-domain, disulfide bond rich basement membrane protein. Mutations in perlecan cause Schwartz-Jampel syndrome and dyssegmental dysplasia. While there has been a large body of experimental work reported on perlecan, there is only minimal structural information available to date. There is no prior structural data for region 3 of perlecan in which some Schwartz-Jampel syndrome causing point mutations have been reported. Here, we produce constructs of the disulfide rich region 3 of perlecan along with five mutations previously reported to cause Schwatz-Jampel syndrome. Four of the mutations resulted in decreased yields and thermal stability compared to the wild-type protein. In contrast, the P1019L mutation was produced in good yields and showed higher thermal stability than the wild-type protein. The crystal structures for both the wild-type and P1019L mutation were solved. As expected, both showed laminin IV-like and laminin-type EGF-like domains, with the P1019L mutation resulting in only a minor conformational change in a loop region and no significant changes in regular secondary or tertiary structure.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"138 ","pages":"Pages 1-7"},"PeriodicalIF":4.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circulating collagen type I fragments as specific biomarkers of cardiovascular outcome risk: Where are the opportunities?

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-02 DOI: 10.1016/j.matbio.2025.03.001

Emily M. Martin , Joan Chang , Arantxa González , Federica Genovese

引用次数: 0

Laminins and the blood-brain barrier

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-03-01 DOI: 10.1016/j.matbio.2025.02.005

Ava Nasrollahi, Yao Yao

{"title":"Laminins and the blood-brain barrier","authors":"Ava Nasrollahi, Yao Yao","doi":"10.1016/j.matbio.2025.02.005","DOIUrl":"10.1016/j.matbio.2025.02.005","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) is a dynamic structure that maintains brain homeostasis. BBB breakdown is a key pathological hallmark of almost all neurological diseases. Although the regulation of BBB integrity by different cells has been extensively studied, the function of its non-cellular component—the basal lamina in BBB regulation remains largely unknown. Laminin, a trimeric protein with multiple isoforms, is one of the most important constituents of the basal lamina. In the CNS, different cells synthesize distinct laminin isoforms, which differentially regulate BBB integrity in both physiological and pathological conditions. A thorough understanding of laminin expression and function in BBB integrity could lead to the identification of novel therapeutic targets and potentially result in effective treatments for neurological disorders involving BBB disruption. Here in this review, we first briefly introduce the BBB and basal lamina with a focus on laminin. Next, we elucidate laminin expression and its function in BBB maintenance/repair in a cell-specific manner. Potential functional compensation among laminin isoforms is also discussed. Last, current challenges in the field and future directions are summarized. Our goal is to provide a synthetic review to encourage novel ideas and stimulate new research in the field.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"137 ","pages":"Pages 33-41"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mysteries of the collagen triple helix

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-02-14 DOI: 10.1016/j.matbio.2025.02.003

Hans Peter Bächinger , Sergei P. Boudko

引用次数: 0

Inhibition of the MRTF-A/SRF signaling axis alleviates vocal fold scarring

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-02-14 DOI: 10.1016/j.matbio.2025.02.004

Ryan M. Friedman , Huy D. Truong , Matthew R. Aronson , Elizabeth A. Brown , Marco Angelozzi , Jeffrey F. Chen , Karen B. Zur , Véronique Lefebvre , Riccardo Gottardi

{"title":"Inhibition of the MRTF-A/SRF signaling axis alleviates vocal fold scarring","authors":"Ryan M. Friedman , Huy D. Truong , Matthew R. Aronson , Elizabeth A. Brown , Marco Angelozzi , Jeffrey F. Chen , Karen B. Zur , Véronique Lefebvre , Riccardo Gottardi","doi":"10.1016/j.matbio.2025.02.004","DOIUrl":"10.1016/j.matbio.2025.02.004","url":null,"abstract":"<div><div>Vocal fold scarring, the most common cause of poor voice after airway injury, involves the transition of vocal fold fibroblasts to contractile myofibroblasts. Vocal fold myofibroblasts can be characterized by significant extracellular matrix (ECM) secretion and stress fiber formation. Biochemical signals, such as transforming growth factor (TGF)-β1, and biophysical cues, such as matrix stiffening, have been shown to induce the fibroblast-to-myofibroblast transition. To identify key intracellular pathways that may mediate myofibroblast activation, we performed bulk RNA sequencing of human vocal fold fibroblasts treated with or without TGF-β1 and found that genes downstream of myocardin related transcription factor A (MRTF-A) and serum response factor (SRF) were upregulated in TGFβ1-induced myofibroblasts. We then show that both TGF-β1 and ECM stiffening induce MRTF-A and SRF nuclear translocation during vocal fold myofibroblast activation. Inhibition of MRTF-A via CCG-257,081 reduced pro-fibrotic gene expression, the percentage of α-smooth muscle actin (α-SMA)-positive fibroblasts, and cell contractility <em>in vitro</em>. In a murine model of vocal fold scarring, MRTF-A inhibition reduced vocal fold scarring severity, evidenced by reduced epithelial thickening, decreased glycosaminoglycan content, and collagen deposition, and decreased expression of <em>ACTA2</em>. Our study suggests that the MRTF-A/SRF pathway regulates vocal fold myofibroblast activation, and that inhibition of MRTF-A has a protective effect against vocal fold scarring in mice.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"137 ","pages":"Pages 1-11"},"PeriodicalIF":4.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of syndecan-4 in angiogenesis and vasculogenic mimicry in triple negative breast cancer cells

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-02-10 DOI: 10.1016/j.matbio.2025.02.002

Jessica Oyie Sousa Onyeisi , Heba M. El-Shorafa , Burkhard Greve , Martin Götte

{"title":"Role of syndecan-4 in angiogenesis and vasculogenic mimicry in triple negative breast cancer cells","authors":"Jessica Oyie Sousa Onyeisi , Heba M. El-Shorafa , Burkhard Greve , Martin Götte","doi":"10.1016/j.matbio.2025.02.002","DOIUrl":"10.1016/j.matbio.2025.02.002","url":null,"abstract":"<div><div>Syndecan-4 (SDC4), a heparan sulfate proteoglycan, is aberrantly expressed in breast cancer and plays a significant role in tumor progression by influencing cell proliferation and promoting invasive growth. This study aimed to characterize its role in the tumor microenvironment by analyzing the contribution of SDC4 to vasculogenic mimicry (VM) and angiogenesis in human breast cancer cells. We silenced SDC4 in the triple-negative breast cancer (TNBC) cell lines MDA-MB-231, MDA-MB-468, and SUM-149 and analyzed its functions in vitro. SDC4 knockdown inhibited the VM of MDA-MB-231 cells as analyzed by fluorescence microscopy. Moreover, RT-qPCR revealed decreased expression of KLF4, EGR1, and HPSE, factors involved in VM, proangiogenic and pro-invasive processes in all TNBC cell lines. Western blotting revealed a partially cell-line-dependent regulation of these proteins by SDC4. At the functional level, SDC4 knockdown also impaired angiogenesis, decreasing the number of nodes and meshes in a 3D co-culture model comprising endothelial cells and TNBC cells. Using a Proteome Profile Human Angiogenesis Array, we observed that SDC4 knockdown decreased the secretion of VEGF and IGFBP-1, while it increased the secretion of IL-8, uPA, and amphiregulin in the conditioned media of the MDA-MB-231 and MDA-MB-468 co-cultures. Independent RT-qPCR analyses of gene expression were consistent with those of the angiogenesis array. Overall, these findings highlighted the crucial role of SDC4 in regulating both vasculogenic mimicry and angiogenesis in TNBC cells. The data indicate that SDC4 acts as a crucial regulatory molecule and represents a promising target for therapeutic strategies in breast cancer.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 127-133"},"PeriodicalIF":4.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dystrophic epidermolysis bullosa - From biochemistry to interventions 萎缩性表皮松解症--从生物化学到干预措施

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-02-06 DOI: 10.1016/j.matbio.2025.02.001

Alexander Nyström

{"title":"Dystrophic epidermolysis bullosa - From biochemistry to interventions","authors":"Alexander Nyström","doi":"10.1016/j.matbio.2025.02.001","DOIUrl":"10.1016/j.matbio.2025.02.001","url":null,"abstract":"<div><div>The skin, as a barrier organ meeting constant mechanical challenges, is equipped with multiple adhesive structures that collectively support resilient, yet flexible attachment of its epithelium –the epidermis to its mesenchyme – the dermis. One such structure is the collagen VII-composed anchoring fibril, which provides firm anchorage of the epidermal basement membrane to the underlying interstitial extracellular matrix. Blistering and wider tissue fragility in the genetic disease dystrophic epidermolysis bullosa (DEB) caused by collagen VII deficiency illustrate the essential function of collagen VII in supporting skin integrity. DEB is also a progressive inflammatory fibrotic disease with multi-organ involvement, indicating that collagen VII has broader functions than simply providing epithelial anchorage. This review explores the reciprocal relationship between collagen VII biology and DEB pathophysiology. A deeper understanding of collagen VII biology – spanning its synthesis, assembly into suprastructures, and regulatory roles – enhances our understanding of DEB. Conversely, detailed insights into DEB through analysis of disease progression or therapeutic interventions offer valuable information on the broader tissue and organismal roles of collagen VII in maintaining homeostasis. This review focuses on such knowledge exchange in advancing our understanding of collagen VII, the extracellular matrix in general, and inspiring potential strategies for treatment of DEB. Importantly, in a broader sense, the discussed themes are applicable to other conditions driven by compromised extracellular matrix instruction and integrity, leading to progressive damage and inflammation.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 111-126"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143369736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: A gene expression study 大疱性结缔组织表皮松解角质形成细胞微环境的改变：一项基因表达研究。

IF 4.5 1区生物学

Matrix Biology Pub Date : 2025-02-01 DOI: 10.1016/j.matbio.2024.11.005

Yao Wang , Maria Elena Hess , Yan Tan , Philipp R. Esser , Alexander Nyström , Melanie Boerries , Saliha Beyza Sayar , Cristina Has

{"title":"Alterations in the microenvironment of junctional epidermolysis bullosa keratinocytes: A gene expression study","authors":"Yao Wang , Maria Elena Hess , Yan Tan , Philipp R. Esser , Alexander Nyström , Melanie Boerries , Saliha Beyza Sayar , Cristina Has","doi":"10.1016/j.matbio.2024.11.005","DOIUrl":"10.1016/j.matbio.2024.11.005","url":null,"abstract":"<div><div>Integrin α6β4 subunits and type XVII collagen are critical transmembrane proteins involved in cell-matrix adhesion in skin, while laminin 332 serves as their ligand in the basement membrane zone (BMZ). Those proteins contribute to the composition of hemidesmosomes (HDs) and pathogenic variants in their corresponding genes cause junctional epidermolysis bullosa (JEB). Although the genotype-phenotype relationships in JEB have been extensively studied, the pathogenetic changes of extracellular matrix (ECM) and cell-matrix adhesion resulting from gene mutations remain unclear. We conducted a global unbiased transcriptome analysis using bulk RNA sequencing (RNA-seq) on selected JEB donor-derived cell lines lacking integrin β4 subunit (ITGB4-), type XVII collagen (COL17-) and laminin β3 chain (LAMB3-), respectively. Additional JEB cell lines and JEB donor skin samples were used for validation of relevant findings. Collectively, the results revealed similar dysregulation patterns of ECM and focal adhesion (FAs) associated genes in ITGB4- and COL17- cell lines, while LAMB3- cells displayed a relatively opposite tendency. Importantly, key nodes in the dysregulated network were associated with ECM proteins involved in wound healing processes. Additionally, a group of inflammatory-associated genes was disclosed to be up-regulated in JEB keratinocytes and could not be normalized by the adhesion rescue. The functional assay further revealed the hierarchy of stable adhesion among mutant cell lines COL17->ITGB4->LAMB3-, which correlates with the severity of their clinical manifestations. Our results indicated a wound healing associated ECM and inflammatory microenvironment established by JEB keratinocytes.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 12-23"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0