Matrix Biology最新文献

{"title":"CD45+/ Col I+ Fibrocytes: Major source of collagen in the fibrotic lung, but not in passaged fibroblast cultures","authors":"Charles F. Reese ,&nbsp;Monika Gooz ,&nbsp;Zoltan Hajdu ,&nbsp;Stanley Hoffman","doi":"10.1016/j.matbio.2025.01.005","DOIUrl":"10.1016/j.matbio.2025.01.005","url":null,"abstract":"<div><div>The role of cells of the hematopoietic lineage in fibrosis is controversial. Here we evaluate the contribution of Col I+/CD45+ cells (fibrocytes) to lung fibrosis. Systemic bleomycin treatment was used to induce fibrosis in a bone marrow transplant and two transgenic mouse models. Lung cells from these mice were analyzed by flow cytometry, both immediately upon release from the tissue or following growth on tissue-culture plastic. Fibrotic and control human lung tissue were also used. Fibroblasts and fibrocytes derived from a transgenic mouse model were compared in terms of their morphology, growth, and adhesion to fibronectin. Single cell RNAseq was performed with the analysis focusing on CD45-/Col <em>I</em>+ “fibroblasts” and CD45+/Col <em>I</em>+ “fibrocytes” in control and fibrotic mouse lung tissue. Finally, we inhibited fibrosis in mice using a novel, water-soluble version of caveolin scaffolding domain (CSD) called WCSD.</div><div>In both mouse and human lung tissue, we observed by flow cytometry a large increase in fibrocyte number and Col I expression associated with fibrosis. In contrast, fibroblast number was not significantly increased. A large increase (&gt;50-fold) in fibrocyte number associated with fibrosis was also observed by single cell RNAseq. In this case, fibroblasts increased 5-fold. Single cell RNAseq also revealed that myofibroblast markers in fibrotic tissue are associated with a cluster containing a similar number of fibrocytes and fibroblasts, not with a resident fibroblast cluster. Some investigators claim that fibrocytes are not present among primary fibroblasts. However, we found that fibrocytes were the predominant cell type present in these cultures prior to passage. Fewer fibrocytes were present after one passage, and almost none after two passages. Our experiments suggest that fibrocytes are crowded out of cultures during passage because fibroblasts have a larger footprint than fibrocytes, even though fibrocytes bind more efficiently to fibronectin. Finally, we observed by flow cytometry that in mice treated with bleomycin and WCSD compared to bleomycin alone, there was a large decrease in the number of fibrocytes present but not in the number of fibroblasts. In summary, fibrocytes are a major collagen-producing cell type that is increased in number in association with fibrosis as well as a major source of myofibroblasts. The common observation that collagen-producing spindle-shaped cells associated with fibrosis are CD45- may be an artifact of passage in cell culture.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 87-101"},"PeriodicalIF":4.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015184","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}

{"title":"Decoding the MMP14 integrin link: Key player in the secretome landscape","authors":"Stephan Niland,&nbsp;Johannes A. Eble","doi":"10.1016/j.matbio.2025.01.004","DOIUrl":"10.1016/j.matbio.2025.01.004","url":null,"abstract":"<div><div>Rapid progress has been made in the exciting field of secretome research in health and disease. The tumor secretome, which is a significant proportion of the tumor proteome, is secreted into the extracellular space to promote intercellular communication and thus tumor progression. Among the many molecules of the secretome, integrins and matrix metalloproteinase 14 (MMP14) stand out as the interplay of adhesion and proteolysis drives invasion. Integrins serve as mechanosensors that mediate the contact of cells with the scaffold of the extracellular matrix and are significantly involved in the precise positioning and activity control of the membrane-bound collagenase MMP14. As a secretome proteinase, MMP14 influences and modifies the secretome itself. While integrins and MT-MMPs are membrane bound, but can be released and are therefore border crossers between the cell surface and the secretome, the extracellular matrix is not constitutively cell-bound, but its binding to integrins and other cell receptors is a stringently regulated process. To understand the mutual interactions in detail, we first summarize the structure and function of MMP14 and how it is regulated at the enzymatic and cellular level. In particular, the mutual interactions between integrins and MMP14 include the proteolytic cleavage of integrins themselves by MMP14. We then review the biochemical, cell biological and physiological effects of MMP14 on the composition and associated functions in the tumor secretome when either bound to the cell membrane, or located on extracellular microvesicles, or as a proteolytically shed non-membrane-bound ectodomain. Novel methods of proteomics, including the analysis of extravesicular vesicles, and new methods for the quantification of MMP14 will provide new research and diagnostic tools. The proteolytic modification of the tumor secretome, especially by MMP14, may bring an additional aspect to tumor secretome studies and will have an impact on the diagnosis and most likely also on the therapy of cancer patients.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 36-51"},"PeriodicalIF":4.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015186","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}

{"title":"Endothelial cell (EC)-specific Ctgf/Ccn2 expression increases EC reprogramming and atherosclerosis","authors":"Feifei Li ,&nbsp;Sandeep Kumar ,&nbsp;Anastassia Pokutta-Paskaleva ,&nbsp;Dong-won Kang ,&nbsp;Chanwoo Kim ,&nbsp;Julia Raykin ,&nbsp;Victor Omojola ,&nbsp;Carson Hoffmann ,&nbsp;Fujie Zhao ,&nbsp;Maiko Teichmann ,&nbsp;Christian Park ,&nbsp;Kyung In Baek ,&nbsp;Gloriani Sanchez Marrero ,&nbsp;Jing Ma ,&nbsp;Hiromi Yanagisawa ,&nbsp;Andrew Leask ,&nbsp;Lucas Timmins ,&nbsp;Xiangqin Cui ,&nbsp;Roy Sutliff ,&nbsp;Rudy L. Gleason Jr. ,&nbsp;Luke P. Brewster","doi":"10.1016/j.matbio.2025.01.003","DOIUrl":"10.1016/j.matbio.2025.01.003","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques. Disturbed flow is pro-inflammatory to ECs. Arteries also stiffen with aging and/or the onset of vascular disease. ECs sense and respond to stiffening in a pro-fibrotic manner. Thus, flow and stiffening disturbances elicit EC responses that promote pathologic arterial remodeling. However, the pathways elicited by ECs under pathologic stiffening and disturbed flow are not well understood.&lt;/div&gt;&lt;div&gt;The objective of this work was to discover and test the modifiability of key pathways in ECs. To do this we used the partial carotid ligation model to impose disturbed flow onto the precociously stiffened fibulin-5 knockout (&lt;em&gt;Fbln5&lt;sup&gt;-/-&lt;/sup&gt;&lt;/em&gt;) mouse carotid arteries. Biomechanical testing demonstrated that &lt;em&gt;Fbln5&lt;sup&gt;-/-&lt;/sup&gt;&lt;/em&gt; arteries under disturbed flow approximate the stiffness ratio of diseased human arteries, and the ECs in these &lt;em&gt;Fbln5&lt;sup&gt;-/-&lt;/sup&gt;&lt;/em&gt; arteries underwent rapid reprogramming via endothelial to mesenchymal transition (EndMT). Under atherogenic conditions, disturbed flow &lt;em&gt;Fbln5&lt;sup&gt;-/-&lt;/sup&gt;&lt;/em&gt; arteries developed more vulnerable plaques than the wild type (WT) mouse arteries. Connective tissue growth factor/cellular communication network factor 2 (&lt;em&gt;Ctgf&lt;/em&gt;/&lt;em&gt;Ccn2&lt;/em&gt;) was upregulated in vivo in ECs with aging, with stiffening in the &lt;em&gt;Fbln5&lt;/em&gt;&lt;sup&gt;-/-&lt;/sup&gt; arteries, and increased again by disturbed flow under stiffened conditions, supporting CTGF as a key biomarker for flow and stiffening. This was validated by immunohistochemistry, which demonstrated increased CTGF deposition in areas of disturbed flow in patient carotid endarterectomy and peripheral artery disease (PAD) specimens. Finally, to test the role of CTGF in regulating and combining these processes, we created an EC-specific &lt;em&gt;Ctgf&lt;/em&gt; knockout (&lt;em&gt;Ctgf&lt;sup&gt;ecko&lt;/sup&gt;&lt;/em&gt;). We identified that carotid arteries under disturbed flow and atherogenic conditions in male &lt;em&gt;Ctgf&lt;sup&gt;ecko&lt;/sup&gt;&lt;/em&gt;, but not female, mice had decreased plaque area compared to WT control mice. We then tested the &lt;em&gt;Ctgf&lt;/em&gt; expression in the carotid endothelium exposed to disturbed or stable flow in WT and &lt;em&gt;Fbln5&lt;sup&gt;-/-&lt;/sup&gt;&lt;/em&gt; mice. Here we found that under disturbed flow male mice had greater &lt;em&gt;Ctgf&lt;/em&gt; expression than female mice.&lt;/div&gt;&lt;div&gt;This work demonstrates that stiffened + disturbed flow conditions drive EC reprogramming, that CTGF is increased by these conditions, and that this increase is more prominent in male carotid arteries. Future exploration of sex-based differences in these fibrotic pathways are warranted to develop targeted therapeutics to limit pathologic arterial remodeling under pathologically stiffened + disturbed flow environments.&lt;/","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 102-110"},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015188","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}

{"title":"The structural organisation of pentraxin-3 and its interactions with heavy chains of inter-α-inhibitor regulate crosslinking of the hyaluronan matrix","authors":"Anokhi Shah ,&nbsp;Xiaoli Zhang ,&nbsp;Matthew Snee ,&nbsp;Michael P. Lockhart-Cairns ,&nbsp;Colin W. Levy ,&nbsp;Thomas A. Jowitt ,&nbsp;Holly L. Birchenough ,&nbsp;Louisa Dean ,&nbsp;Richard Collins ,&nbsp;Rebecca J. Dodd ,&nbsp;Abigail R.E. Roberts ,&nbsp;Jan J. Enghild ,&nbsp;Alberto Mantovani ,&nbsp;Juan Fontana ,&nbsp;Clair Baldock ,&nbsp;Antonio Inforzato ,&nbsp;Ralf P. Richter ,&nbsp;Anthony J. Day","doi":"10.1016/j.matbio.2025.01.002","DOIUrl":"10.1016/j.matbio.2025.01.002","url":null,"abstract":"<div><div>Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) of the inter-α-inhibitor (IαI) family of proteoglycans are covalently attached, playing a key role in the (non-covalent) crosslinking of HC•HA complexes. These interactions stabilise the cumulus matrix, essential for ovulation and fertilisation in mammals, and are also implicated in the formation of pathogenic matrices in the context of viral lung infections. To better understand the physiological and pathological roles of PTX3 we have analysed how its quaternary structure underpins HA crosslinking via its interactions with HCs. A combination of X-ray crystallography, cryo-electron microscopy (cryo-EM) and AlphaFold predictive modelling revealed that the C-terminal pentraxin domains of the PTX3 octamer are arranged in a central cube, with two long extensions on either side, each formed from four protomers assembled into tetrameric coiled-coil regions, essentially as described by (Noone <em>et al</em>., 2022; doi:10.1073/pnas.2208144119). From crystallography and cryo-EM data, we identified a network of inter-protomer salt bridges that facilitate the assembly of the octamer. Small angle X-ray scattering (SAXS) validated our model for the octameric protein, including the analysis of two PTX3 constructs: a tetrameric ‘Half-PTX3’ and a construct missing the 24 N-terminal residues (Δ1–24_PTX3). SAXS determined a length of ∼520 Å for PTX3 and, combined with 3D variability analysis of cryo-EM data, defined the flexibility of the N-terminal extensions. Biophysical analyses revealed that the prototypical heavy chain HC1 does not interact with PTX3 at pH 7.4, consistent with our previous studies showing that, at this pH, PTX3 only associates with HC•HA complexes if they are formed in its presence. However, PTX3 binds to HC1 at acidic pH, and can also be incorporated into pre-formed HC•HA complexes under these conditions. This provides a novel mechanism for the regulation of PTX3-mediated HA crosslinking (e.g., during inflammation), likely mediated by a pH-dependent conformational change in HC1. The PTX3 octamer was found to associate simultaneously with up to eight HC1 molecules and, thus, has the potential to form a major crosslinking node within HC•HA matrices, i.e., where the physical and biochemical properties of resulting matrices could be tuned by the HC/PTX3 composition.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 52-68"},"PeriodicalIF":4.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015211","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}

{"title":"Neurocan regulates axon initial segment organization and neuronal activity","authors":"David Baidoe-Ansah ,&nbsp;Hadi Mirzapourdelavar ,&nbsp;Stepan Aleshin ,&nbsp;Björn Hendrik Schott ,&nbsp;Constanze Seidenbecher ,&nbsp;Rahul Kaushik ,&nbsp;Alexander Dityatev","doi":"10.1016/j.matbio.2025.01.001","DOIUrl":"10.1016/j.matbio.2025.01.001","url":null,"abstract":"<div><div>The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability. Here, we used knockdown and knockout approaches in mouse primary cortical neurons in combination with immunocytochemistry, Western blotting and electrophysiological techniques to characterize the role of Ncan in the organization of PNNs and AISs and regulation of neuronal activity. We found that reduced Ncan levels led to remodeling of PNNs around neurons via upregulation of aggrecan mRNA and protein levels, increased expression of activity-dependent c-Fos and FosB genes and elevated spontaneous synaptic activity. The latter correlated with increased levels of ankyrin-G in the AIS, particularly in excitatory neurons, and with the elevated expression of Na_v1.6 channels. Our results suggest that Ncan regulates the expression of key proteins in PNNs and AISs and provide new insights into its role in fine-tuning neuronal functions.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 22-35"},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957983","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}

{"title":"FGF and TGF-β growth factor isoform modulation of human gingival and periodontal ligament fibroblast wound healing phenotype","authors":"Chengyu Guo ,&nbsp;Amin S. Rizkalla ,&nbsp;Douglas W. Hamilton","doi":"10.1016/j.matbio.2024.12.011","DOIUrl":"10.1016/j.matbio.2024.12.011","url":null,"abstract":"<div><div>Release of growth factors in the tissue microenvironment is a critical process in the repair and regeneration of periodontal tissues, regulating fibroblast behavior and phenotype. As a result of the complex architecture of the periodontium, distinct fibroblast populations in the periodontal ligament and gingival connective tissue exist in close proximity. Growth factor therapies for periodontal regeneration have gained traction, but quantification of their effects on multiple different fibroblast populations that are required for repair has been poorly investigated. In this study, we examined the effects of TGF-β1, TGF-β3, FGF-2, and FGF-9 on human gingival fibroblasts (hGF) and human periodontal ligament cells (hPDL), as well as the combined effects of TGF-β3 and FGF-2. We show that FGF-2 enhances cell migration while TGF-β1 and TGF-β3 promotes matrix production, and TGF-β1 promotes fibroblast to myofibroblast transition. Interestingly, the combination of TGF-β3 and FGF-2, acting through both p-SMAD3 and p-ERK pathways, mitigates the inhibitory effects of TGF-β3 on migration in hPDL cells, suggesting synergistic and complimentary effects of FGF-2 and TGF-β3. Additionally, fibronectin production in hGF increased when treated with the combined TGF-β3+FGF-2 compared to FGF-2 alone, indicating that the effects of TGF-β3 in promoting extracellular matrix production are still active in the combined treatment condition. Finally, our study highlights that FGF-9 did not influence migration, α-SMA expression, or extracellular matrix production in either cell type, emphasizing the unique roles of specific growth factors in cellular responses. The synergistic effects observed with combined TGF-β3 and FGF-2 treatments present promising avenues for further research and clinical advancements in regenerative medicine.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 9-21"},"PeriodicalIF":4.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933403","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}

{"title":"35k Da specific-sized hyaluronan ameliorates high-fat diet-induced liver injury in murine model of moderate obesity","authors":"Semanti Ray ,&nbsp;Emily Huang ,&nbsp;Megan R McMullen ,&nbsp;Samreen Jatana ,&nbsp;Carol de la Motte ,&nbsp;Laura E Nagy","doi":"10.1016/j.matbio.2024.12.010","DOIUrl":"10.1016/j.matbio.2024.12.010","url":null,"abstract":"<div><div>Obesity is a growing concern in the US and world-wide, associated with an increased risk for several cardiometabolic diseases, including metabolic associated steatotic liver disease (MASLD). Currently, therapeutic interventions to prevent and/or treat MASLD are limited, and research is needed to identify new therapeutic targets. The specific-sized 35 kDa fragment of hyaluronan (HA35), has gut protective and anti-inflammatory properties and a previous pilot clinical study reported it is well tolerated in healthy individuals. Here we tested the hypothesis that HA35 treatment ameliorates high fat diet-induced liver injury. Five-week-old male C57BL/6 J mice were allowed <em>ad lib</em> access to control chow or high fat fructose and cholesterol (FFC) diet over a period of 12 weeks. HA35 was administered at 15mg/kg via oral gavage on the last 6 days of the study as a therapeutic intervention. Mice on FFC diet-gained more body weight compared to those on chow diet, with final body weights ranging from 30.8 to 45.6 g. FFC diet caused hepatocyte injury, increased expression of inflammatory cytokine/chemokine mRNA, as well as indicators of liver fibrosis. When mice were stratified based on their final body weight, only mice &lt;40 g were protected by treatment with HA35. In this group, treatment with HA35 also restored tight junction integrity in the colon and increased expression of α -defensins in the small intestine. Taken together the data suggests that HA35 is an effective therapeutic in ameliorating high fat diet-induced liver inflammation and fibrosis in moderately obese, but not severe, conditions.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"136 ","pages":"Pages 1-8"},"PeriodicalIF":4.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899974","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}

{"title":"Identification of CD44 as a key engager to hyaluronic acid-rich extracellular matrices for cell traction force generation and tumor invasion in 3D","authors":"Brian C.H. Cheung ,&nbsp;Xingyu Chen ,&nbsp;Hannah J. Davis ,&nbsp;Cassidy S. Nordmann ,&nbsp;Joshua Toth ,&nbsp;Louis Hodgson ,&nbsp;Jeffrey E. Segall ,&nbsp;Vivek B. Shenoy ,&nbsp;Mingming Wu","doi":"10.1016/j.matbio.2024.11.004","DOIUrl":"10.1016/j.matbio.2024.11.004","url":null,"abstract":"<div><div>Mechanical properties of the extracellular matrix (ECM) critically regulate a number of important cell functions including growth, differentiation and migration. Type I collagen and glycosaminoglycans (GAGs) are two primary components of ECMs that contribute to mammalian tissue mechanics, with the collagen fiber network sustaining tension, and GAGs withstanding compression. The architecture and stiffness of the collagen network are known to be important for cell-ECM mechanical interactions via cell surface adhesion receptor integrin. In contrast, studies of GAGs in modulating cell-ECM interactions are limited. Here, we present experimental studies on the roles of hyaluronic acid (HA) in single tumor cell traction force generation using a recently developed 3D cell traction force microscopy method. Our work reveals that CD44, a cell surface receptor to HA, is engaged in cell traction force generation in conjunction with β1-integrin. We find that HA significantly modifies the architecture and mechanics of the collagen fiber network, decreasing tumor cells’ propensity to remodel the collagen network, attenuating traction force generation, transmission distance, and tumor invasion. Our findings point to a novel role for CD44 in traction force generation, which can be a potential therapeutic target for diseases involving HA rich ECMs such as breast cancer and glioblastoma.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"135 ","pages":"Pages 1-11"},"PeriodicalIF":4.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631368","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}

{"title":"Remodeling of the extracellular matrix by serine proteases as a prerequisite for cancer initiation and progression","authors":"Tomasz Wenta ,&nbsp;Paulina Nastaly ,&nbsp;Barbara Lipinska ,&nbsp;Aki Manninen","doi":"10.1016/j.matbio.2024.10.007","DOIUrl":"10.1016/j.matbio.2024.10.007","url":null,"abstract":"<div><div>The extracellular matrix (ECM) serves as a physical scaffold for tissues that is composed of structural proteins such as laminins, collagens, proteoglycans and fibronectin, forming a three dimensional network, and a wide variety of other matrix proteins with ECM-remodeling and signaling functions. The activity of ECM-associated signaling proteins is tightly regulated. Thus, the ECM serves as a reservoir for water and growth regulatory signals. The ECM architecture is dynamically modulated by multiple serine proteases that process both structural and signaling proteins to regulate physiological processes such as organogenesis and tissue homeostasis but they also contribute to pathological events, especially cancer progression. Here, we review the current literature regarding the role of ECM remodeling by serine proteases (KLKs, uPA, furin, HtrAs, granzymes, matriptase, hepsin) in tumorigenesis.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 197-219"},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584786","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}

{"title":"The epidermal integrin-mediated secretome regulates the skin microenvironment during tumorigenesis and repair","authors":"Whitney M. Longmate","doi":"10.1016/j.matbio.2024.11.002","DOIUrl":"10.1016/j.matbio.2024.11.002","url":null,"abstract":"<div><div>Integrins are cellular transmembrane receptors that physically connect the cytoskeleton with the extracellular matrix. As such, they are positioned to mediate cellular responses to microenvironmental cues. Importantly, integrins also regulate their own microenvironment through secreted factors, also known as the integrin-mediated secretome. Epidermal integrins, or integrins expressed by keratinocytes of the skin epidermis, regulate the cutaneous microenvironment through the contribution of matrix components, via proteolytic matrix remodeling, or by mediating factors like cytokines and growth factors that can promote support for nearby but distinct cells of the stroma, such as immune cells, endothelial cells, and fibroblasts. This role for integrins is enhanced during both pathological and repair tissue remodeling processes, such as tumor growth and progression and wound healing. This review will discuss examples of how the epithelial integrin-mediated secretome can regulate the tissue microenvironment. Although different epithelial integrins in various contexts will be explored, emphasis will be given to epidermal integrins that regulate the secretome during wound healing and cutaneous tumor progression. Epidermal integrin α3β1 is of particular focus as well, since this integrin has been revealed as a key regulator of the keratinocyte secretome.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 175-183"},"PeriodicalIF":4.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567833","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}