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Oxygen and TGF-β1 jointly regulate fibronectin and trophoblast behavior highlighting a potential role for matrix signalingin severe preeclampsia 氧和TGF-β1共同调节纤维连接蛋白和滋养细胞的行为,这突出了基质信号在重度子痫前期的潜在作用
IF 6.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-31 DOI: 10.1016/j.matbio.2026.01.002
Felipe Gallardo, Delia I. Chiarello, Ivo Carrasco-Wong, Sebastián San Martín, Andrea Leiva, Rocío Salsoso, Jaime Gutiérrez
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引用次数: 0
An integrin α3β1-CSTF3 signaling axis regulates alternative polyadenylation of Mmp9 mRNA 整合素α3β1-CSTF3信号轴调控Mmp9 mRNA的选择性聚腺苷化
IF 6.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-31 DOI: 10.1016/j.matbio.2026.01.003
Giesse Albeche Duarte, Ramon Bossardi Ramos, Lei Wu, Whitney M. Longmate, C. Michael DiPersio
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引用次数: 0
Amelogenin proteolysis orchestrates functional amyloid pathways in enamel development 淀粉原蛋白水解在牙釉质发育过程中调控淀粉样蛋白通路
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-11 DOI: 10.1016/j.matbio.2026.01.001
Emerson Tavares de Sousa , Larry Ackerman , Johan Svensson Bonde , Stefan Habelitz , Yushi Bai
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 in vivo 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.
成釉原蛋白是发育中的牙釉质中最丰富的蛋白质,它可以自我组装成超分子结构,作为磷灰石生长的模板。最近的研究表明,淀粉原纳米带具有功能性淀粉样蛋白的标志性特征,但控制其形成的分子机制仍不完全清楚。在这里,我们结合原子力显微镜、透射电子显微镜和光谱分析来确定全长淀粉原蛋白(rH174)及其由金属蛋白酶-20 (MMP20)产生的主要蛋白水解产物的组装途径。研究表明,rH174和c端截断的rH146都遵循成核构象转换机制,从球形低聚物经过原带到有序的富含β片的纳米带。rH174的组装过程缓慢,表现为滞后期延长和成熟期延迟,而rH146的成核速度很快,在较短的时间内完成这些阶段。将rH146交叉播种到rH174单体中(1:10),消除了rH174组装的延迟,迅速推动了系统的延伸,并导致了组装系统的早期稳定。在rH174中,c端驱动的相互作用触发二次成核,演变成类似珐琅质组织的捆绑纳米带,这一过程在rH146中基本不存在。因此,交叉播种体现了体内机制,即新生的淀粉原蛋白立即添加到现有的纳米带支架中,这是一种产生异质基质的合作策略,结合了快速成核和空间组织的能力。出乎意料的是,MMP20切割产物- TRAP,包含交叉β组装结构域,在c端水解时不形成纳米带,偏离全长淀粉原蛋白的组装途径。因此,存在一种mmp20驱动的机制,可以促进牙釉质基质作为间隔物,并在成釉发生的分泌阶段阻止早期晶体融合。这些发现为蛋白质水解引发的组装途径提供了新的见解,该途径可能会调和长期存在的淀粉原蛋白超分子模型,并将淀粉原蛋白建立为脊椎动物的功能性淀粉样蛋白,可以调节以实现有序的牙釉质生物矿化。
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引用次数: 0
An interview with Valerie Horsley 瓦莱丽·霍斯利的采访
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-23 DOI: 10.1016/j.matbio.2025.12.004
Valerie Horsley
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引用次数: 0
Follow the science: How fat cells taught us about scarring and ECM homeostasis 遵循科学:脂肪细胞如何教会我们疤痕和ECM稳态
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-15 DOI: 10.1016/j.matbio.2025.12.003
Valerie Horsley
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.
这篇文章描述了我的实验室团队的旅程,因为我们对组织损伤和纤维化期间皮肤脂肪组织发生的动态变化着迷。我讨论了谱系追踪和脂肪细胞谱系细胞的分子操作如何引导我们发现脂肪细胞促进皮肤ECM稳态的新途径。这项工作揭示了脂肪细胞可塑性和细胞通讯在组织修复过程中的重要性,以及它们对纤维化刺激的反应。
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引用次数: 0
α-Dystroglycan at the ECM-Cell crossroad: emerging functions of its N-terminal domain α-异糖甘蛋白在ECM-Cell十字路口:其n端结构域的新功能
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-11 DOI: 10.1016/j.matbio.2025.12.002
Maria Giulia Bigotti , Andrea Brancaccio
Dystroglycan plays a crucial role for cell to extracellular matrix (ECM) adhesiveness in a plethora of different tissues and physio-pathological conditions. It belongs to the dystrophin-glycoprotein complex, whose overall structure has been recently solved, providing fundamental insight into the assembly of its various protein components, including the dystroglycan complex. This inspired us to embark in a timely “recollection journey” of our studies on the dystroglycan domain organization, mainly focusing on the targeted mutagenesis analysis of the α-dystroglycan’s N-terminal domain (α-DGN) that we have carried out during the last 30 years. The account of such a journey also reinforces a crucial notion in protein biochemistry: a single amino acid substitution can lead to a significantly improved stability of the whole protein. Over-stabilizing matrix proteins, and proteins in general, has positive repercussions for the study of their structural and functional properties, and it is a crucial tool for developing biotechnological applications. Here we discuss newly emerged data along a series of yet unresolved points concerning the biochemical features and biological role of α-DGN, as well as the possible biomedical use recently emerged for a stabilized single site-directed variant of this protein domain.
歧义糖聚糖在多种不同组织和生理病理条件下对细胞与细胞外基质(ECM)的粘附性起着至关重要的作用。它属于肌营养不良蛋白-糖蛋白复合物,其整体结构最近已被解决,为其各种蛋白质成分的组装提供了基本的见解,包括糖营养不良复合物。这启发了我们及时地开始了我们对糖醛酸异常结构域组织研究的“回忆之旅”,主要集中在我们近30年来进行的α-糖醛酸异常结构域n端(α-DGN)的靶向诱变分析。对这一过程的描述也强化了蛋白质生物化学中的一个重要概念:单个氨基酸的替换可以显著提高整个蛋白质的稳定性。过度稳定的基质蛋白和一般的蛋白质对其结构和功能特性的研究具有积极的影响,是开发生物技术应用的重要工具。在这里,我们讨论了关于α-DGN的生化特征和生物学作用的一系列尚未解决的新数据,以及该蛋白结构域稳定的单位点定向变体最近出现的可能的生物医学用途。
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引用次数: 0
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 肝脏来源的循环血浆纤维连接蛋白调节成年雄性小鼠的骨小梁骨量和骨形成,以及其在血清中的水平与老年男性骨密度的关系
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-07 DOI: 10.1016/j.matbio.2025.12.001
Mahdokht Mahmoodi , Claudie Berger , Mir-Hamed Nabavi , Yongjun Xiao , Lucie Canaff , Monica Pata , Jingjing Li , Mathieu Ferron , Monzur Murshed , David Goltzman , Suzanne N. Morin , Mari T. Kaartinen
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 in vitro studies, but in vivo 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 (Fn1-/-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 (CaMos) biobank demonstrated that circulating plasma fibronectin levels were significantly higher in men versus 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, p=0.0088), and of the total hip (p=0.0066) strongly suggesting an association between pFN levels and fracture risk in men.
血浆纤维连接蛋白是一种来源于肝脏的糖蛋白,它以较高的浓度循环并在组织中积累形成ECM。血浆纤维连接蛋白在成骨细胞发生、骨形成和重塑中的作用已被许多体外研究提出,但在小鼠体内模型中尚未证实其在骨形成和骨量维持中的作用。在这项研究中,我们对成年、6个月大的雄性和雌性肝细胞特异性纤维连接蛋白敲除(Fn1-/- alb)小鼠进行了骨骼表型分析。我们报道,通过胫骨和椎小梁骨的微计算机断层扫描(μCT)分析,小鼠骨量明显减少。双能x线骨密度测量显示骨密度降低。椎体骨的组织形态学分析显示成骨细胞和矿物质附着率显著降低;血清骨形成标志物(PINP)也显著降低,表明血浆纤维连接蛋白在成年小鼠成骨细胞形成中起重要作用。该表型仅在雄性小鼠中观察到。破骨细胞生成未受影响。通过加拿大多中心骨质疏松研究(CaMos)生物库对人类骨质疏松症患者血浆纤维连接蛋白水平的分析表明,50岁及以上男性的循环血浆纤维连接蛋白水平明显高于女性。男性骨质疏松患者血浆纤维连接蛋白水平明显降低,这与低骨密度值、腰椎(L1-4, p=0.0088)和全髋关节(p=0.0066)的t评分降低相关,强烈提示pFN水平与男性骨折风险之间存在关联。
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引用次数: 0
Human mammary 3D spheroid models uncover the role of filopodia in breaching the basement membrane to facilitate invasion 人类乳腺三维球体模型揭示了丝状足在突破基底膜以促进入侵中的作用
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.matbio.2025.11.008
Alain Corinus , Sophie Abélanet , Julia Dubreuil , Zhenyu Zhu , Sabrina Pisano , Christelle Boscagli , Anne-Sophie Gay , Delphine Debayle , Marin Truchi , Kevin Lebrigand , Sandra Lacas-Gervais , Frédéric Brau , Xavier Descombes , Patricia Rousselle , Michel Franco , Frédéric Luton
Basement membranes (BM) are thin, nanoporous sheets of specialized extracellular matrix (ECM) that line epithelial tissues. They are dynamic structures that serve multiple key functions, as evidenced by numerous diseases, including cancer progression, that are associated with their alterations. Our understanding of the BM and its communication with adjoining epithelial cells remains highly fragmented due to the BM’s complex molecular architecture, the lack of molecular tools, limitations in utilizing high-resolution imaging techniques to BMs assembled on tissues, and the difficulty of assessing their functional contributions in vivo. Here, by combining multiple -omics analyses and advanced microscopy methodologies, we characterized the BM from two normal human mammary epithelial cell lines, MCF10 and HMLE, grown as spheroids in 3D matrices. Our findings indicate that the spheroids autonomously assemble a BM exhibiting all the molecular, structural, and biophysical characteristics of physiological BM. Using these minimalist model systems, we provide evidence that collagen IV, laminins, perlecan, and hemidesmosomes all overlap in a shared porous lattice. Next, we demonstrate that the invasion-promoting PSD4/EFA6B knockout, found in patients with breast cancer, decreases the expression of BM components and their assembly on the spheroid surface. We then show that invasive spheroids develop enlarged pores in the BM via filopodia-like plasma membrane extensions, which further expand in a protease-dependent manner, thereby facilitating the passage of invasive cells.
基底膜(BM)是排列在上皮组织上的细胞外基质(ECM)的薄的纳米多孔薄片。它们是具有多种关键功能的动态结构,正如许多疾病(包括癌症进展)所证明的那样,与它们的改变有关。由于脑基的复杂分子结构,缺乏分子工具,利用高分辨率成像技术对组织上组装的脑基的限制,以及难以评估其在体内的功能贡献,我们对脑基及其与邻近上皮细胞的通讯的理解仍然高度分散。在这里,通过结合多组学分析和先进的显微镜方法,我们对两种正常人类乳腺上皮细胞系MCF10和HMLE的BM进行了表征,这些细胞系在3D基质中作为球体生长。我们的研究结果表明,这些球体自主组装成一个BM,展示了生理BM的所有分子、结构和生物物理特征。使用这些极简模型系统,我们提供了证据,证明胶原蛋白IV,层粘连蛋白,perlecan和半脂粒都在一个共享的多孔晶格中重叠。接下来,我们证明在乳腺癌患者中发现的促进侵袭的PSD4/EFA6B基因敲除降低了BM组分的表达及其在球体表面的组装。然后,我们发现侵入性球体通过丝状足样质膜延伸在基底膜中形成扩大的孔,这些孔以蛋白酶依赖的方式进一步扩大,从而促进了侵入性细胞的通过。
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引用次数: 0
Retraction Notice to “RETRACTED: The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis” “撤回:血管抑制分子Multimerin 2被MMP-9处理以允许发芽血管生成”的撤回通知。
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.matbio.2025.10.002
Eva Andreuzzi , Roberta Colladel , Rosanna Pellicani , Giulia Tarticchio , Renato Cannizzaro , Paola Spessotto , Benedetta Bussolati , Alessia Brossa , Paolo De Paoli , Vincenzo Canzonieri , Renato V. Iozzo , Alfonso Colombatti , Maurizio Mongiat
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引用次数: 0
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] “laminin -511功能化纤维蛋白凝胶使人诱导多能干细胞在凝胶内增殖”的勘误表[Matrix Biology Volume 142, December 2025, Pages 21-32]
IF 4.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-11-29 DOI: 10.1016/j.matbio.2025.11.005
Yukimasa Taniguchi, Mamoru Takizawa, Ayaka Hada, Ayano Ishimaru, Kiyotoshi Sekiguchi
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引用次数: 0
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