Matrix Biology最新文献

{"title":"Breast cancer cells with decreased fibronectin-integrin adhesion strength attenuate the malignancy of its microenvironment","authors":"Natalia Burday, Gemma Guerrero-Barberà, Asier Jayo, Manuel M. Sánchez del Pino, Elena Ortiz-Zapater, Mercedes Costell","doi":"10.1016/j.matbio.2026.102067","DOIUrl":"https://doi.org/10.1016/j.matbio.2026.102067","url":null,"abstract":"","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"1 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149232157","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":"Amelogenin proteolysis orchestrates functional amyloid pathways in enamel development","authors":"Emerson Tavares de Sousa ,&nbsp;Larry Ackerman ,&nbsp;Johan Svensson Bonde ,&nbsp;Stefan Habelitz ,&nbsp;Yushi Bai","doi":"10.1016/j.matbio.2026.01.001","DOIUrl":"10.1016/j.matbio.2026.01.001","url":null,"abstract":"<div><div>Amelogenin, the most abundant protein in developing enamel, self-assembles into supramolecular structures that serve as templates for apatite growth. Recent studies revealed that amelogenin nanoribbons exhibit hallmark features of functional amyloids, yet the molecular mechanisms governing their formation remain incompletely understood. Here, we combine atomic force microscopy, transmission electron microscopy, and spectroscopic analyses to define the assembly pathways of full-length amelogenin (rH174) alongside its major proteolytic products generated by metalloproteinase-20 (MMP20). We demonstrate that both rH174 and the C-terminally truncated rH146 follow a nucleated conformational conversion mechanism, progressing from spherical oligomers through proto-ribbons to ordered β-sheet–rich nanoribbons. rH174 assembly progresses slowly, displaying an extended lag phase and delayed maturation, whereas rH146 nucleates rapidly, completing these stages within a shorter timeframe. Cross-seeding of rH146 into rH174 monomers (1:10) eliminates the delay in rH174 assembly, rapidly driving the system into elongation and leading to an earlier stabilization of the assembly system. C-terminus–driven interactions in rH174 trigger secondary nucleation that evolves into bundled nanoribbons resembling enamel organization, a process largely absent in rH146. Cross-seeding, therefore, exemplifies the <em>in vivo</em> mechanism whereby nascent amelogenin is immediately added to existing nanoribbon scaffolds, a cooperative strategy that generates a heterogeneous matrix, coupling the ability of rapid nucleation and spatial organization. Unexpectedly, the MMP20 cleavage product – TRAP, which comprises the cross-beta assembly domain, does not form nanoribbons and diverts from the assembly pathway full-length amelogenin takes when hydrolyzed at the C-terminal. Hence, a MMP20-driven mechanism exists that could contribute to an enamel matrix that acts as a spacer and prevents early crystal fusion during the secretory stage of amelogenesis. These findings offer insights into a proteolysis-triggered assembly pathway that may reconcile long-standing supramolecular models of amelogenin and establish amelogenin as a vertebrate example of a functional amyloid that can be tuned to enable ordered enamel biomineralization.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"144 ","pages":"Pages 1-12"},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956867","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":"Oxygen and TGF-β1 jointly regulate fibronectin and trophoblast behavior highlighting a potential role for matrix signaling in severe preeclampsia","authors":"Felipe Gallardo ,&nbsp;Delia I. Chiarello ,&nbsp;Ivo Carrasco-Wong ,&nbsp;Sebastián San Martín ,&nbsp;Andrea Leiva ,&nbsp;Rocío Salsoso ,&nbsp;Jaime Gutiérrez","doi":"10.1016/j.matbio.2026.01.002","DOIUrl":"10.1016/j.matbio.2026.01.002","url":null,"abstract":"<div><div>Fibronectin is a key component of the extracellular matrix whose abundance and organization depend on both environmental conditions and intracellular signaling. In this study we show that oxygen tension modifies the response of extravillous trophoblasts to TGF-β1 and thereby controls fibronectin output and matrix dependent cell behavior. TGF-β1 increased fibronectin transcripts and protein through SMAD3, p38 and AKT, while hypoxia altered this response by reducing fibronectin protein despite preserved mRNA and by shifting downstream phosphorylation toward SMAD3, ERK and p38 with reduced AKT activity. These changes influenced functional outcomes: fibronectin rich conditions and TGF-β1 suppressed invasion and supported endothelial-like organization, and interference with fibronectin integrin binding preserved invasiveness and prevented network formation. Analysis of placental tissue showed that the spatial pattern of fibronectin expression differs in severe preeclampsia, where fibronectin appears earlier along the trophoblast trajectory compared with normal pregnancy. Together, these findings define how oxygen and TGF-β1 jointly regulate fibronectin and trophoblast behavior, while descriptive observations in human placental tissue provide histological context consistent with these cellular responses and suggest a potential role for matrix-associated signaling in severe preeclampsia.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"144 ","pages":"Pages 13-25"},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095746","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":"An integrin α3β1-CSTF3 signaling axis regulates alternative polyadenylation of Mmp9 mRNA","authors":"Giesse Albeche Duarte ,&nbsp;Ramon Bossardi Ramos ,&nbsp;Lei Wu ,&nbsp;Whitney M. Longmate ,&nbsp;C. Michael DiPersio","doi":"10.1016/j.matbio.2026.01.003","DOIUrl":"10.1016/j.matbio.2026.01.003","url":null,"abstract":"<div><div>The laminin-binding integrin α3β1 is highly expressed in epidermal keratinocytes, where it coordinates diverse cellular functions and gene expression during skin remodeling. Here, we show that α3β1-MEK/ERK signaling operates <em>in vivo</em> to promote proximal polyadenylation site (PAS) usage in the <em>Mmp9</em> gene, generating a short, more stable mRNA transcript. Using mice with inducible, epidermis-specific α3 deletion, RNA <em>in situ</em> hybridization revealed that loss of α3β1 increased the long <em>Mmp9</em> transcript in healing wounds and epidermal tumors. α3β1-MEK/ERK signaling in keratinocytes induced the expression of the cleavage stimulation factor CSTF3, a known regulator of alternative polyadenylation (APA), while CSTF3 knockdown shifted <em>Mmp9</em> toward distal PAS usage. Moreover, α3 deletion reduced <em>Cstf3</em> gene expression and altered APA <em>in vivo</em>. Genome-wide DaPars2 analysis identified α3β1-dependent APA across numerous genes, including some encoding components of the keratinocyte secretome. Together, these findings define a novel α3β1-MEK/ERK-CSTF3 axis that orchestrates post-transcriptional gene regulation through APA, revealing α3β1 as a potential target for wound and cancer therapies.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"144 ","pages":"Pages 26-37"},"PeriodicalIF":4.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095744","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":"Furin-like cleavage at the C1-C2 linker region of the ⍺3 chain is not required for collagen VI assembly","authors":"Arthur Lauri Pasanen-Zentz ,&nbsp;Mengjie Zhu ,&nbsp;Sebastian Schmitz ,&nbsp;Nitin George Eapen ,&nbsp;Matthias Pzryklenk ,&nbsp;Fabian Metzen ,&nbsp;Karina Hadrian ,&nbsp;Matthias Mörgelin ,&nbsp;Uwe Hansen ,&nbsp;Branko Zevnik ,&nbsp;Simon E Tröder ,&nbsp;Felix Bock ,&nbsp;Catherine Moali ,&nbsp;Marcus Krüger ,&nbsp;Manuel Koch ,&nbsp;Mats Paulsson ,&nbsp;Raimund Wagener ,&nbsp;Alvise Schiavinato","doi":"10.1016/j.matbio.2025.11.003","DOIUrl":"10.1016/j.matbio.2025.11.003","url":null,"abstract":"<div><div>Collagen VI is a heterotrimeric, ubiquitously expressed microfibrillar collagen with a complex intracellular and extracellular assembly process. In addition to a short collagenous region, it is primarily composed of von Willebrand factor A (VWA) domains. Notably, only the C-terminal end of the α3 chain contains other domain types, including a Kunitz-like C5 domain, which has been reported to be necessary for microfibril formation, to function as a matrikine and exhibit biomarker properties. This region of the α3 chain undergoes proteolytic processing, with cleavage sites identified for proprotein convertases, matrix metalloproteinases (MMPs), and bone morphogenetic protein 1 (BMP1). Cleavage by furin-like convertases results in the generation of a mature collagen VI α3 chain lacking its 70 kDa C2-C5 domains. Here, we provide the first characterization of the functional significance of the furin-like cleavage site, demonstrating that while it is constitutively used, it is not essential for collagen VI assembly, microfibril formation, or skeletal muscle function under physiological conditions, likely due to the presence of redundant cleavage sites. We also present an initial characterization of the biological activity of the released fragments on myoblast cultures showing that they do not affect C2C12 myoblast behaviour or differentiation. These findings deepen our understanding of α3 chain processing and highlight its potential significance for collagen VI assembly and function, including the generation of peptides with potential biomarker and biological activity properties.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Pages 1-13"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531347","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":"Follow the science: How fat cells taught us about scarring and ECM homeostasis","authors":"Valerie Horsley","doi":"10.1016/j.matbio.2025.12.003","DOIUrl":"10.1016/j.matbio.2025.12.003","url":null,"abstract":"<div><div>This article describes the journey of my laboratory team as we became fascinated with the dynamic changes that occurred to adipose tissue in the skin during tissue injury and fibrosis. I discuss how lineage tracing and molecular manipulation of adipocyte lineage cells led us to discover novel ways that fat cells contribute to ECM homeostasis in the skin. This work revealed the importance of adipocyte plasticity and cell communication during tissue repair and as they respond to fibrotic stimuli.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Pages 89-91"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760382","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":"Zebrafish col4a1 loss-of-function models mirror key neurovascular and ocular features of COL4A1/A2 syndrome and enable human variants assessment in vivo","authors":"Graziamaria Paradisi ,&nbsp;Valeria Bonavolontà ,&nbsp;Martina Venditti ,&nbsp;Giulia Fasano ,&nbsp;Catia Pedalino ,&nbsp;Filippo Del Bene ,&nbsp;Marco Tartaglia ,&nbsp;Antonella Lauri","doi":"10.1016/j.matbio.2025.11.004","DOIUrl":"10.1016/j.matbio.2025.11.004","url":null,"abstract":"<div><div>Pathogenic variants in <em>COL4A1</em> and <em>COL4A2</em>, encoding type IV collagen α1 and α2 chains—core components of all basement membranes—cause a multisystem disorder with variable expressivity. Affected individuals commonly present with cerebral small vessel disease (cSVD), unmanageable intracerebral haemorrhage (ICH), drug-resistant epilepsy, microphthalmia, and congenital cataract. Severe phenotypes are often linked to glycine substitutions that disrupt α1/α2 heterotrimer assembly, though insertions, deletions, and haploinsufficiency seem to also be pathogenic. Limited insight into collagen IV α1 and α2 biology and how specific variants affect their functions—coupled with a lack of rapid <em>in vivo</em> assays for functional variants classification—hampers patient stratification and therapy development. Here, we established and characterized two complementary <em>col4a1</em> knockdown (KD) models in zebrafish. Taking advantages of their transparency and rapid development we set-up <em>in vivo</em> assays for neurovascular and ocular phenotyping. Both models reproduced key features of human disease, including ventriculomegaly, vascular fragility with spontaneous and trauma-induced ICH, microphthalmia, and cataracts. Notably, expression of human wild-type COL4A1 partially rescued most of the observed defects, while pathogenic glycine-substitution variants failed to do so. These findings validate <em>col4a1</em> KD in zebrafish as a robust <em>in vivo</em> model of some aspects of COL4A1/A2 syndrome, highlighting a conserved role of collagen IV α1 in neurovascular and ocular development. Our results also support haploinsufficiency as a contributing pathogenic mechanism, alongside dominant-negative effects. This work lays the foundation for the use of zebrafish to support rapid <em>COL4A1</em> and <em>COL4A2</em> variants pathogenicity assessment and mechanistic studies, with the potential to accelerate development of targeted therapies.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Pages 63-82"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531352","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":"Liver-derived, circulating plasma fibronectin regulates trabecular bone mass and bone formation in adult male mice and its levels in sera associates with bone density in aging men","authors":"Mahdokht Mahmoodi ,&nbsp;Claudie Berger ,&nbsp;Mir-Hamed Nabavi ,&nbsp;Yongjun Xiao ,&nbsp;Lucie Canaff ,&nbsp;Monica Pata ,&nbsp;Jingjing Li ,&nbsp;Mathieu Ferron ,&nbsp;Monzur Murshed ,&nbsp;David Goltzman ,&nbsp;Suzanne N. Morin ,&nbsp;Mari T. Kaartinen","doi":"10.1016/j.matbio.2025.12.001","DOIUrl":"10.1016/j.matbio.2025.12.001","url":null,"abstract":"<div><div>Plasma fibronectin is a liver-derived glycoprotein that circulates at relatively high concentration and accumulates in tissues to form ECM. The role of plasma fibronectin in osteoblastogenesis, bone formation and remodeling has been suggested by many <em>in vitro</em> studies, but <em>in vivo</em> mouse models have not confirmed its role in bone formation and maintenance of bone mass. In this study we have performed skeletal phenotyping of adult, 6-month-old male and female, hepatocyte-specific fibronectin knockout (<em>Fn1</em>-/-ALB) mice. We report that mice have a significant loss of bone mass as analyzed by micro-Computed Tomography (μCT) of the tibial and vertebral trabecular bone. Dual-energy X-ray absorptiometry of the vertebral bone showed a decrease in bone mineral density. Histomorphometric analysis of bone cell numbers in vertebral bone showed a significant decrease in osteoblasts and in mineral apposition rates; there was also a significant reduction of a serum marker of bone formation (PINP), demonstrating an important role for plasma fibronectin in osteoblastogenesis in adult mice. The phenotype was observed only in male mice. Osteoclastogenesis was not affected. Analysis of plasma fibronectin levels in human osteoporosis via Canadian Multicentre Osteoporosis Study (CaM<em>os</em>) biobank demonstrated that circulating plasma fibronectin levels were significantly higher in men <em>versus</em> women aged 50 and over. Male osteoporotic patients showed significantly lower plasma fibronectin levels which correlated with low bone mineral density values, and with reduced T-scores of the lumbar spine (L1-4, <em>p</em>=0.0088), and of the total hip <em>(p</em>=0.0066) strongly suggesting an association between pFN levels and fracture risk in men.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Pages 48-62"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689366","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":"Corrigendum to “Laminin-511-functionalized fibrin gel enables in-gel proliferation of human induced pluripotent stem cells” [Matrix Biology Volume 142, December 2025, Pages 21–32]","authors":"Yukimasa Taniguchi,&nbsp;Mamoru Takizawa,&nbsp;Ayaka Hada,&nbsp;Ayano Ishimaru,&nbsp;Kiyotoshi Sekiguchi","doi":"10.1016/j.matbio.2025.11.005","DOIUrl":"10.1016/j.matbio.2025.11.005","url":null,"abstract":"","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Pages 18-22"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613994","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":"An interview with Valerie Horsley","authors":"Valerie Horsley","doi":"10.1016/j.matbio.2025.12.004","DOIUrl":"10.1016/j.matbio.2025.12.004","url":null,"abstract":"","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"143 ","pages":"Page 92"},"PeriodicalIF":4.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823742","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}