Pub Date : 2025-07-28DOI: 10.1016/j.matbio.2025.07.007
Matilda Thuringer , Roy Zent , Rachel Lennon , Erin J. Plosa
The primary function of the respiratory system is the exchange of oxygen and carbon dioxide across the alveolar-capillary barrier in the distal lung. This structure is composed of alveolar epithelial cells (type 1 and type 2) and capillary endothelial cells, separated by a thin, fused alveolar basement membrane. The developmental programming that creates this specialized niche is largely unexplored and the role of lung basement membranes in respiratory disease pathogenesis and repair remains an emerging field of study. Thus, in this review, we discuss the distribution, composition, and function of the alveolar basement membrane, as well as the other three lung basement membranes that support the airway epithelium, airway smooth muscles, and the endothelium of the macrovasculature in lung development and disease.
{"title":"Basement membranes in lung development, disease, and repair","authors":"Matilda Thuringer , Roy Zent , Rachel Lennon , Erin J. Plosa","doi":"10.1016/j.matbio.2025.07.007","DOIUrl":"10.1016/j.matbio.2025.07.007","url":null,"abstract":"<div><div>The primary function of the respiratory system is the exchange of oxygen and carbon dioxide across the alveolar-capillary barrier in the distal lung. This structure is composed of alveolar epithelial cells (type 1 and type 2) and capillary endothelial cells, separated by a thin, fused alveolar basement membrane. The developmental programming that creates this specialized niche is largely unexplored and the role of lung basement membranes in respiratory disease pathogenesis and repair remains an emerging field of study. Thus, in this review, we discuss the distribution, composition, and function of the alveolar basement membrane, as well as the other three lung basement membranes that support the airway epithelium, airway smooth muscles, and the endothelium of the macrovasculature in lung development and disease.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 123-132"},"PeriodicalIF":4.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754962","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}
Collagen is an essential skin protein, accounting for 75 % of the skin’s dry weight. The collagen superfamily encompasses a diverse group of proteins with a variety of structures that fulfil a wide range of functions. The half-life of collagen in the skin is generally estimated at 10 to 15 years; however, the expression pattern of the different types of skin collagen varies throughout life. Both intrinsic and extrinsic factors influence collagen turn-over within the different skin layers. In this review, we discuss current knowledge of the different types of collagen present in human skin, focusing on insights gained from research exploring the dynamic roles of these proteins in skin development, homeostasis including aging, collagen-linked pathologies, adaptability in response to stress, and wound healing-related processes and disorders. Specificities of skin diversity due to ancestral origin and gender will also be discussed.
{"title":"Collagen diversity in human skin: Aging, wound healing, and disorders","authors":"Mélanie Salamito , Valérie Haydont , Hervé Pageon , Florence Ruggiero , Sarah Girardeau-Hubert","doi":"10.1016/j.matbio.2025.07.006","DOIUrl":"10.1016/j.matbio.2025.07.006","url":null,"abstract":"<div><div>Collagen is an essential skin protein, accounting for 75 % of the skin’s dry weight. The collagen superfamily encompasses a diverse group of proteins with a variety of structures that fulfil a wide range of functions. The half-life of collagen in the skin is generally estimated at 10 to 15 years; however, the expression pattern of the different types of skin collagen varies throughout life. Both intrinsic and extrinsic factors influence collagen turn-over within the different skin layers. In this review, we discuss current knowledge of the different types of collagen present in human skin, focusing on insights gained from research exploring the dynamic roles of these proteins in skin development, homeostasis including aging, collagen-linked pathologies, adaptability in response to stress, and wound healing-related processes and disorders. Specificities of skin diversity due to ancestral origin and gender will also be discussed.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 133-153"},"PeriodicalIF":4.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144734955","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}
Pub Date : 2025-07-22DOI: 10.1016/j.matbio.2025.07.005
Angus Nichols, Besaiz J. Sánchez-Sánchez, Stefania Marcotti, María-del-Carmen Díaz-de-la-Loza, Leonel C. Menezes, Tingfei Wang, Robert M. Johnson, Brian M. Stramer
Collagen IV (Col4) is a heterotrimer containing a triple helical domain broken up by short interruptions. Mutation of Glycine residues within the Glycine-X-Y triple helical repeat leads to genetically dominant disease in humans that affects multiple organ systems. Mouse and cell culture-based models have revealed allelic heterogeneity, resulting in a range of Col4 secretion defects depending on the position of the mutation. However, genetic background also affects phenotypic severity, making it challenging to understand the precise underlying molecular mechanisms driving disease. Here, we characterize an allelic series of dominant temperature-sensitive Drosophila Glycine mutations to identify the potential molecular mechanisms driving phenotypic heterogeneity. Analysis of developmental viability at the non-permissive temperature revealed that mutations show a range of developmental lethality that is not correlated with their position within the triple helix nor with the degree of Col4 secretion defect. Backcrossing the series of fly lines led to increased lethality for almost all alleles, highlighting the presence of genetic modifiers, which paradoxically led to a reduction in secretion defects; this further suggests that defective secretion cannot explain the allelic heterogeneity in mutant viability. Analysis of the Col4 network surrounding the central nervous system (CNS) revealed that Glycine mutations can also affect basement membrane (BM) structure and alter its mechanical properties. Additionally, fluorescent tagging of a Glycine mutant variant showed that the mutated trimer is sufficiently secreted and can be incorporated into the network to dominantly affect BM organization. These data reveal that Col4 Glycine mutations can cause both secretion and direct BM network defects, suggesting that Col4-related pathologies may be mechanistically pleiotropic.
胶原IV （Col4）是一种含有三螺旋结构域的异源三聚体，该结构域由短中断断开。甘氨酸- x - y三螺旋重复序列中甘氨酸残基的突变导致人类遗传显性疾病，影响多器官系统。基于小鼠和细胞培养的模型揭示了等位基因的异质性，导致Col4分泌缺陷的范围取决于突变的位置。然而，遗传背景也会影响表型的严重程度，这使得理解驱动疾病的精确潜在分子机制具有挑战性。在这里，我们描述了一系列显性温度敏感的果蝇甘氨酸突变的等位基因，以确定驱动表型异质性的潜在分子机制。在非允许温度下的发育活力分析表明，突变显示出一系列的发育致死率，这与它们在三螺旋中的位置无关，也与Col4分泌缺陷的程度无关。蝇系系列的回交导致几乎所有等位基因的致死率增加，突出了遗传修饰的存在，这矛盾地导致了分泌缺陷的减少；这进一步表明分泌缺陷不能解释突变体活力的等位基因异质性。对中枢神经系统（CNS）周围Col4网络的分析表明，甘氨酸突变也可以影响基底膜（BM）结构并改变其力学性能。此外，甘氨酸突变变体的荧光标记表明，突变的三聚体分泌充足，可以被纳入网络，主要影响BM组织。这些数据表明Col4甘氨酸突变既可以引起分泌缺陷，也可以引起直接的BM网络缺陷，这表明Col4相关的病理可能是多效性的。
{"title":"Drosophila Col4a1 Glycine mutations highlight allelic heterogeneity and mechanistic pleiotropy","authors":"Angus Nichols, Besaiz J. Sánchez-Sánchez, Stefania Marcotti, María-del-Carmen Díaz-de-la-Loza, Leonel C. Menezes, Tingfei Wang, Robert M. Johnson, Brian M. Stramer","doi":"10.1016/j.matbio.2025.07.005","DOIUrl":"10.1016/j.matbio.2025.07.005","url":null,"abstract":"<div><div>Collagen IV (Col4) is a heterotrimer containing a triple helical domain broken up by short interruptions. Mutation of Glycine residues within the Glycine-X-Y triple helical repeat leads to genetically dominant disease in humans that affects multiple organ systems. Mouse and cell culture-based models have revealed allelic heterogeneity, resulting in a range of Col4 secretion defects depending on the position of the mutation. However, genetic background also affects phenotypic severity, making it challenging to understand the precise underlying molecular mechanisms driving disease. Here, we characterize an allelic series of dominant temperature-sensitive <em>Drosophila</em> Glycine mutations to identify the potential molecular mechanisms driving phenotypic heterogeneity. Analysis of developmental viability at the non-permissive temperature revealed that mutations show a range of developmental lethality that is not correlated with their position within the triple helix nor with the degree of Col4 secretion defect. Backcrossing the series of fly lines led to increased lethality for almost all alleles, highlighting the presence of genetic modifiers, which paradoxically led to a reduction in secretion defects; this further suggests that defective secretion cannot explain the allelic heterogeneity in mutant viability. Analysis of the Col4 network surrounding the central nervous system (CNS) revealed that Glycine mutations can also affect basement membrane (BM) structure and alter its mechanical properties. Additionally, fluorescent tagging of a Glycine mutant variant showed that the mutated trimer is sufficiently secreted and can be incorporated into the network to dominantly affect BM organization. These data reveal that Col4 Glycine mutations can cause both secretion and direct BM network defects, suggesting that Col4-related pathologies may be mechanistically pleiotropic.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 113-122"},"PeriodicalIF":4.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700161","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}
Pub Date : 2025-07-15DOI: 10.1016/j.matbio.2025.06.003
K. Yanín Guerra Santillán, Christian Dahmann, Elisabeth Fischer-Friedrich
The basal surface of epithelial tissues is attached to a thin network of macromolecules known as the basement membrane. The core components of the basement membrane — Collagen IV, Laminin, Perlecan, and Nidogen — are conserved extracellular matrix (ECM) proteins across species. However, the topography of basement membranes and the contribution of individual core components to its establishment remain poorly understood. Here, we used AFM-aided PeakForce tapping to analyze the topography of the basement membrane of Drosophila larval wing discs. We identified a self-affine surface topography, appearing structurally similar across multiple scales. Further, the topography is characterized by thin fiber-like structures that are intermittently aligned with a preferred orientation along the anterior-posterior axis. During larval development, the amplitude of surface patterns overall decreases, whereas the abundance of basement membrane components increases. Using targeted knockdown experiments, we show that Collagen IV is essential for the formation of fiber-like structures, while Laminin and Collagen IV appear to smooth or level out large-scale groove-like patterns. In contrast, Nidogen contributes to the maintenance of these grooves, and Perlecan increases surface pattern amplitudes at all length scales. Our findings reveal distinct topographical features in the basement membrane, whose amplitude and organization depend on its specific molecular composition.
{"title":"ECM proteins shape topographical patterns in the basement membrane of Drosophila wing discs","authors":"K. Yanín Guerra Santillán, Christian Dahmann, Elisabeth Fischer-Friedrich","doi":"10.1016/j.matbio.2025.06.003","DOIUrl":"10.1016/j.matbio.2025.06.003","url":null,"abstract":"<div><div>The basal surface of epithelial tissues is attached to a thin network of macromolecules known as the basement membrane. The core components of the basement membrane — Collagen IV, Laminin, Perlecan, and Nidogen — are conserved extracellular matrix (ECM) proteins across species. However, the topography of basement membranes and the contribution of individual core components to its establishment remain poorly understood. Here, we used AFM-aided PeakForce tapping to analyze the topography of the basement membrane of <em>Drosophila</em> larval wing discs. We identified a self-affine surface topography, appearing structurally similar across multiple scales. Further, the topography is characterized by thin fiber-like structures that are intermittently aligned with a preferred orientation along the anterior-posterior axis. During larval development, the amplitude of surface patterns overall decreases, whereas the abundance of basement membrane components increases. Using targeted knockdown experiments, we show that Collagen IV is essential for the formation of fiber-like structures, while Laminin and Collagen IV appear to smooth or level out large-scale groove-like patterns. In contrast, Nidogen contributes to the maintenance of these grooves, and Perlecan increases surface pattern amplitudes at all length scales. Our findings reveal distinct topographical features in the basement membrane, whose amplitude and organization depend on its specific molecular composition.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 78-87"},"PeriodicalIF":4.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655501","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}
The hallmark of amyloid diseases is deposition of misfolded proteins as amyloid fibrils in the interstitium of target organs. Amyloid deposits surround cells, distorting the micro and macro-architecture of the extracellular space and profoundly changing the physical and molecular properties of this compartment. In the heart, extracellular matrix (ECM) remodeling has a profound impact on the mechanical properties of this target organ and on the physiology and metabolism of resident cells. This review critically summarizes the available knowledge on ECM alterations in cardiac amyloidosis, with the goal of providing an overview on how biochemical, biophysical and anatomical modifications are interrelated, and how ECM remodeling participates in the pathophysiology of this unique type of cardiopathy.
{"title":"Role of extracellular space and matrix remodeling in cardiac amyloidosis","authors":"Francesca Lavatelli , Loredana Marchese , Palma Patrizia Mangione , Sara Raimondi , Diana Canetti , Guglielmo Verona , Lucia Venneri , Eloisa Arbustini , Laura Obici , Alessandra Corazza , Vittorio Bellotti , Sofia Giorgetti","doi":"10.1016/j.matbio.2025.07.004","DOIUrl":"10.1016/j.matbio.2025.07.004","url":null,"abstract":"<div><div>The hallmark of amyloid diseases is deposition of misfolded proteins as amyloid fibrils in the interstitium of target organs. Amyloid deposits surround cells, distorting the micro and macro-architecture of the extracellular space and profoundly changing the physical and molecular properties of this compartment. In the heart, extracellular matrix (ECM) remodeling has a profound impact on the mechanical properties of this target organ and on the physiology and metabolism of resident cells. This review critically summarizes the available knowledge on ECM alterations in cardiac amyloidosis, with the goal of providing an overview on how biochemical, biophysical and anatomical modifications are interrelated, and how ECM remodeling participates in the pathophysiology of this unique type of cardiopathy.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 100-112"},"PeriodicalIF":4.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622477","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}
Pub Date : 2025-07-09DOI: 10.1016/j.matbio.2025.07.001
Alana Stevenson Harris , Rachel Lennon , Jean-Marc Schwartz
Basement membranes (BMs) are dense extracellular matrix scaffolds that support cells. Their composition, structure and dynamic regulation are vital for tissue health and altered in human disease. The expansion of experimental and analytical techniques has generated large multiomic datasets that include BM components; however, the organising principles of BM component assembly and the regulation of BMs remain poorly understood. There are over 160 curated BM proteins, including core, ubiquitous components such as type IV collagen and laminin isoforms, as well as tissue-restricted components, and there is increasing experimental evidence of BM protein-protein interactions. Here we describe and compare multiomic, protein-protein interaction, and BM curation databases and discuss the application of systems biology approaches including network analysis, Boolean networks and Ordinary Differential Equations to integrate data and model BM organisation. Applying computational modelling strategies to BM datasets may reveal unknown organising principles of BM assembly and regulation and predict mechanisms of dysregulation in BM-associated diseases.
{"title":"Building basement membranes with computational approaches","authors":"Alana Stevenson Harris , Rachel Lennon , Jean-Marc Schwartz","doi":"10.1016/j.matbio.2025.07.001","DOIUrl":"10.1016/j.matbio.2025.07.001","url":null,"abstract":"<div><div>Basement membranes (BMs) are dense extracellular matrix scaffolds that support cells. Their composition, structure and dynamic regulation are vital for tissue health and altered in human disease. The expansion of experimental and analytical techniques has generated large multiomic datasets that include BM components; however, the organising principles of BM component assembly and the regulation of BMs remain poorly understood. There are over 160 curated BM proteins, including core, ubiquitous components such as type IV collagen and laminin isoforms, as well as tissue-restricted components, and there is increasing experimental evidence of BM protein-protein interactions. Here we describe and compare multiomic, protein-protein interaction, and BM curation databases and discuss the application of systems biology approaches including network analysis, Boolean networks and Ordinary Differential Equations to integrate data and model BM organisation. Applying computational modelling strategies to BM datasets may reveal unknown organising principles of BM assembly and regulation and predict mechanisms of dysregulation in BM-associated diseases.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 88-99"},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621006","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}
Pub Date : 2025-07-07DOI: 10.1016/j.matbio.2025.07.003
Sergei P. Boudko
The triple helix structure of collagen is the most abundant motif found in our bodies. It is believed to have emerged during the transition from unicellular to multicellular animal organisms, known as metazoans, and has evolved into various proteins that contribute to the development and function of diverse animal tissues, organs, and systems. Once synthesized, these collagenous proteins undergo post-translational modifications and proper folding inside the cell, after which they primarily function outside the cell. Over 80 collagenous proteins are categorized into two main groups: collagens and collagen-like proteins. However, the distinction between these groups is not clearly defined. Within these categories, there are various types of proteins, including soluble proteins, transmembrane proteins, and those that form the extracellular matrix. Multiple genetic diseases highlight the significance of collagenous proteins, which can be affected by defects in their primary structure, post-translational modifications, or complete loss. While fixing the gene defect may seem like a straightforward solution, we currently lack the capability to do so. Moreover, acquired diseases caused or accompanied by adverse processes in the collagen triple helix are generally not suitable for gene therapy at all. Understanding the pathogenicity of a defective polypeptide chain can provide valuable insights into strategies for mitigating negative consequences for both genetic and acquired diseases. This review highlights the current state of research in the collagen triple helix field, offering insights into how to study specific defects and deepen our understanding of their underlying pathogenic mechanisms.
{"title":"Around the collagen triple helix: an introduction to studying associated genetic and acquired diseases","authors":"Sergei P. Boudko","doi":"10.1016/j.matbio.2025.07.003","DOIUrl":"10.1016/j.matbio.2025.07.003","url":null,"abstract":"<div><div>The triple helix structure of collagen is the most abundant motif found in our bodies. It is believed to have emerged during the transition from unicellular to multicellular animal organisms, known as metazoans, and has evolved into various proteins that contribute to the development and function of diverse animal tissues, organs, and systems. Once synthesized, these collagenous proteins undergo post-translational modifications and proper folding inside the cell, after which they primarily function outside the cell. Over 80 collagenous proteins are categorized into two main groups: collagens and collagen-like proteins. However, the distinction between these groups is not clearly defined. Within these categories, there are various types of proteins, including soluble proteins, transmembrane proteins, and those that form the extracellular matrix. Multiple genetic diseases highlight the significance of collagenous proteins, which can be affected by defects in their primary structure, post-translational modifications, or complete loss. While fixing the gene defect may seem like a straightforward solution, we currently lack the capability to do so. Moreover, acquired diseases caused or accompanied by adverse processes in the collagen triple helix are generally not suitable for gene therapy at all. Understanding the pathogenicity of a defective polypeptide chain can provide valuable insights into strategies for mitigating negative consequences for both genetic and acquired diseases. This review highlights the current state of research in the collagen triple helix field, offering insights into how to study specific defects and deepen our understanding of their underlying pathogenic mechanisms.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 43-58"},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602117","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}
Pub Date : 2025-07-04DOI: 10.1016/j.matbio.2025.07.002
Yoshihiro Ishikawa , Rachel Lennon , Federico Forneris , Johanna Myllyharju , Antti M. Salo
Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified proteins. Despite substantial research on fibrillar collagen biosynthesis, our understanding of collagen IV biosynthesis, including its post-translational modifications (PTMs), remains limited. Most PTMs occur intracellularly, primarily within the endoplasmic reticulum (ER). In this review, we examine the molecular ensemble that orchestrates collagen IV biosynthesis in the ER, highlighting the complex interplay between prolyl and lysyl hydroxylases, glycosyltransferases, and molecular chaperones. Furthermore, we discuss how defects in collagen IV and its PTMs contribute to various human pathologies, including Gould and Alport syndromes, fibrosis, and cancer. Understanding collagen IV PTMs is crucial for elucidating the molecular basis of these diseases and improving targeted treatments. By reviewing our knowledge of collagen IV biosynthesis, we illustrate how this evolutionarily conserved yet highly specialized molecular biosynthesis ensemble supports the diverse functions of collagen IV in health and disease.
{"title":"Collagen IV biosynthesis: Intracellular choreography of post-translational modifications","authors":"Yoshihiro Ishikawa , Rachel Lennon , Federico Forneris , Johanna Myllyharju , Antti M. Salo","doi":"10.1016/j.matbio.2025.07.002","DOIUrl":"10.1016/j.matbio.2025.07.002","url":null,"abstract":"<div><div>Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified proteins. Despite substantial research on fibrillar collagen biosynthesis, our understanding of collagen IV biosynthesis, including its post-translational modifications (PTMs), remains limited. Most PTMs occur intracellularly, primarily within the endoplasmic reticulum (ER). In this review, we examine the molecular ensemble that orchestrates collagen IV biosynthesis in the ER, highlighting the complex interplay between prolyl and lysyl hydroxylases, glycosyltransferases, and molecular chaperones. Furthermore, we discuss how defects in collagen IV and its PTMs contribute to various human pathologies, including Gould and Alport syndromes, fibrosis, and cancer. Understanding collagen IV PTMs is crucial for elucidating the molecular basis of these diseases and improving targeted treatments. By reviewing our knowledge of collagen IV biosynthesis, we illustrate how this evolutionarily conserved yet highly specialized molecular biosynthesis ensemble supports the diverse functions of collagen IV in health and disease.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 59-77"},"PeriodicalIF":4.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576776","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}
Pub Date : 2025-06-14DOI: 10.1016/j.matbio.2025.06.002
George Maiti , Jihane Frikeche , Cynthia Loomis , Michael Cammer , Stephanie L Eichman , Shukti Chakravarti
Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node, known to regulate innate immune myeloid cells, but have not been investigated in lymphoid cell regulations in ACD. By immunohistology we localized lumican and biglycan in skin biopsies of psoriatic patients. Using wild type (WT), lumican and biglycan knockout mice, we investigated CD4+T cell infiltration, activation and proliferation in the skin and draining lymph node (dLN) of contact hypersensitivity (CHS)-challenged mice by immunohistochemistry and flow cytometry. We used the OT-II adoptive transfer model to test antigen specific CD4+T cell activation. We assessed interactions of the proteoglycans with LFA-1 on T cells by confocal microscopy. Compared to WTs, the knockouts showed severe ear inflammation, with increased CD4+T cells infiltration in the dermis. CHS-challenged knockout mice dLN showed increased T-bet, STAT1 and -STAT4 signaling, indicating enhanced Th1 commitment and proliferation. We found that WT lymph node fibroblastic reticular cells (FRCs) secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. Lumican and biglycan interact with LFA-1 on T cell surfaces, and in vitro all three proteoglycans suppress CD4+T cell activation. Secreted by dLN FRCs, lumican, biglycan, and possibly decorin interact with LFA-1 on CD4+T cells to restrict their activation and reduce dermatitis severity.
{"title":"Paracrine regulations of IFN-γ secreting CD4+ T cells by lumican and biglycan are protective in allergic contact dermatitis","authors":"George Maiti , Jihane Frikeche , Cynthia Loomis , Michael Cammer , Stephanie L Eichman , Shukti Chakravarti","doi":"10.1016/j.matbio.2025.06.002","DOIUrl":"10.1016/j.matbio.2025.06.002","url":null,"abstract":"<div><div>Allergic contact dermatitis (ACD) is a delayed-type IV hypersensitivity response driven by innate and adaptive immune cells. While specific immune regulations of these cell types are amply elucidated, their regulations by extracellular matrix (ECM) components and T cell mediated adaptive immunity in ACD remains unclear. Lumican and biglycan are ECM proteoglycans abundant in the dermis and lymph node, known to regulate innate immune myeloid cells, but have not been investigated in lymphoid cell regulations in ACD. By immunohistology we localized lumican and biglycan in skin biopsies of psoriatic patients. Using wild type (WT), lumican and biglycan knockout mice, we investigated CD4<sup>+</sup>T cell infiltration, activation and proliferation in the skin and draining lymph node (dLN) of contact hypersensitivity (CHS)-challenged mice by immunohistochemistry and flow cytometry. We used the OT-II adoptive transfer model to test antigen specific CD4<sup>+</sup>T cell activation. We assessed interactions of the proteoglycans with LFA-1 on T cells by confocal microscopy. Compared to WTs, the knockouts showed severe ear inflammation, with increased CD4<sup>+</sup>T cells infiltration in the dermis. CHS-challenged knockout mice dLN showed increased T-bet, STAT1 and -STAT4 signaling, indicating enhanced Th1 commitment and proliferation. We found that WT lymph node fibroblastic reticular cells (FRCs) secrete lumican, biglycan and decorin, a related proteoglycan, while none are expressed by naive or activated T cells. Lumican and biglycan interact with LFA-1 on T cell surfaces, and <em>in vitro</em> all three proteoglycans suppress CD4<sup>+</sup>T cell activation. Secreted by dLN FRCs, lumican, biglycan, and possibly decorin interact with LFA-1 on CD4<sup>+</sup>T cells to restrict their activation and reduce dermatitis severity.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"140 ","pages":"Pages 27-42"},"PeriodicalIF":4.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289819","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}
Pub Date : 2025-06-13DOI: 10.1016/j.matbio.2025.06.001
Mitchell T. Anderson , Sally Horne-Badovinac
Basement membranes (BMs) are planar extracellular matrices that line the basal surfaces of epithelia and are essential components of most organs. During development, BMs can also play instructive roles in shaping the tissues to which they belong, but how they do so is incompletely understood. The Drosophila egg chamber has become a premier system to study this aspect of BM biology due to the ostensible simplicity of the BM’s role in morphogenesis. The prevailing model posits that the egg chamber’s outer layer of epithelial cells creates a symmetric stiffness gradient in the surrounding BM that preferentially channels egg chamber growth along one axis to create the elongated shape of the egg. There is evidence that the stiffening of the BM depends, in part, on a polarized array of fibrils that form within the BM network, and yet the exact role the BM fibrils play in egg chamber elongation has remained unclear. Here, we use genetic conditions that abrogate fibril formation to different extents to probe the relationship between the BM’s fibril content, its mechanical properties, and the shape of the egg. The results of these experiments are consistent with a model in which BM fibrils influence egg shape by directly augmenting the mechanical properties of the BM. However, we then examine a final genetic condition that does not fit this simple narrative. We propose that the role of the BM in conferring final egg shape is more complicated than previously thought and that some approaches used to study this role should be re-evaluated for their efficacy.
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