Matrix Biology最新文献

{"title":"A lysyl oxidase-responsive collagen peptide illuminates collagen remodeling in wound healing","authors":"Paul Hiebert ,&nbsp;Giuseppe Antoniazzi ,&nbsp;Matthew Aronoff ,&nbsp;Sabine Werner ,&nbsp;Helma Wennemers","doi":"10.1016/j.matbio.2024.02.006","DOIUrl":"10.1016/j.matbio.2024.02.006","url":null,"abstract":"<div><p>Tissue repair and fibrosis involve the dynamic remodeling of collagen, and accurate detection of these sites is of utmost importance. Here, we use a collagen peptide sensor (<strong>1</strong>) to visualize collagen formation and remodeling during wound healing in mice and humans. We show that the probe binds selectively to sites of collagen formation and remodeling at different stages of healing. Compared to conventional methods, the peptide sensor localizes preferentially to areas of collagen synthesis and remodeling at the wound edge and not in matured fibrillar collagen. We also demonstrate its applicability for <em>in vivo</em> wound imaging and for discerning differential remodeling in wounds of transgenic mice with altered collagen dynamics. Our findings show the value of <strong>1</strong> as a diagnostic tool to rapidly identify the sites of matrix remodeling in tissue sections, which will aid in the conception of new therapeutic strategies for fibrotic disorders and defective tissue repair.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"128 ","pages":"Pages 11-20"},"PeriodicalIF":6.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24000258/pdfft?md5=9c7f01eb15a3e7eb570c79764f015938&pid=1-s2.0-S0945053X24000258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139916920","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 adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix","authors":"Johanna Lena Schön ,&nbsp;Victoria Elisabeth Groß ,&nbsp;Willem Berend Post ,&nbsp;Alexandra Daum ,&nbsp;Daniel Matúš ,&nbsp;Johanna Pilz ,&nbsp;Rene Schnorr ,&nbsp;Susanne Horn ,&nbsp;Miriam Bäumers ,&nbsp;Stefanie Weidtkamp-Peters ,&nbsp;Samantha Hughes ,&nbsp;Torsten Schöneberg ,&nbsp;Simone Prömel","doi":"10.1016/j.matbio.2024.02.005","DOIUrl":"10.1016/j.matbio.2024.02.005","url":null,"abstract":"<div><p>The extracellular matrix (ECM) is a network of macromolecules that presents a vital scaffold for cells and enables multiple ways of cellular communication. Thus, it is essential for many physiological processes such as development, tissue morphogenesis, homeostasis, the shape and partially the size of the body and its organs. To ensure these, the composition of the ECM is tissue-specific and highly dynamic. ECM homeostasis is therefore tightly controlled by several mechanisms.</p><p>Here, we show that FMI-1, the homolog of the Adhesion GPCR Flamingo/CELSR/ADGRC in the nematode <em>Caenorhabditis elegans</em>, modulates the composition of the ECM by controlling the production both of ECM molecules such as collagens and also of ECM modifying enzymes. Thereby, FMI-1 affects the morphology and functionality of the nematode´s cuticle, which is mainly composed of ECM, and also modulates the body size. Mechanistic analyses highlight the fact that FMI-1 exerts its function from neurons non-cell autonomously (<em>trans</em>) solely via its extracellular N terminus. Our data support a model, by which the activity of the receptor, which has a well-described role in the planar cell polarity (PCP) pathway, involves the PCP molecule VANG-1, but seems to be independent of the DBL-1/BMP pathway.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"128 ","pages":"Pages 1-10"},"PeriodicalIF":6.9,"publicationDate":"2024-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24000246/pdfft?md5=a8bd278d8e87c1f01e376f3063d345f1&pid=1-s2.0-S0945053X24000246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913960","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":"Dysfunctional latent transforming growth factor β activation after corneal injury in a classical Ehlers–Danlos model","authors":"Mei Sun ,&nbsp;Ana Carolina Acosta ,&nbsp;Victoria Emerick ,&nbsp;Sheila Adams ,&nbsp;Marcel Y Avila ,&nbsp;Curtis E Margo ,&nbsp;Edgar M Espana","doi":"10.1016/j.matbio.2024.02.004","DOIUrl":"10.1016/j.matbio.2024.02.004","url":null,"abstract":"<div><p>Patients with classical Ehlers Danlos syndrome (cEDS) suffer impaired wound healing and from scars formed after injuries that are atrophic and difficult to close surgically. Haploinsufficiency in COL5A1 creates systemic morphological and functional alterations in the entire body. We investigated mechanisms that impair wound healing from corneal lacerations (full thickness injuries) in a mouse model of cEDS (<em>Col5a1</em>^+/−). We found that collagen V reexpression in this model is upregulated during corneal tissue repair and that wound healing is delayed, impaired, and results in large atrophic corneal scars. We noted that in a matrix with a 50 % content of collagen V, activation of latent Transforming Growth Factor (TGF) β is dysregulated. Corneal myofibroblasts with a haploinsufficiency of collagen V failed to mechanically activate latent TGF β. Second harmonic imaging microscopy showed a disorganized, undulated, and denser collagen matrix in our <em>Col5a1</em>^+/- model that suggested alterations in the extracellular matrix structure and function. We hypothesize that a regenerated collagen matrix with only 50 % content of collagen V is not resistant enough mechanically to allow adequate activation of latent TGF β by fibroblasts and myofibroblasts.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"128 ","pages":"Pages 21-30"},"PeriodicalIF":6.9,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716562","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":"Keratinocyte integrin α3β1 induces expression of the macrophage stimulating factor, CSF-1, through a YAP/TEAD-dependent mechanism.","authors":"Whitney M. Longmate ,&nbsp;Emily Norton ,&nbsp;Giesse Albeche Duarte ,&nbsp;Lei Wu ,&nbsp;Mathieu R. DiPersio ,&nbsp;John M. Lamar ,&nbsp;C. Michael DiPersio","doi":"10.1016/j.matbio.2024.02.003","DOIUrl":"10.1016/j.matbio.2024.02.003","url":null,"abstract":"<div><p>The development of wound therapy targeting integrins is hampered by inadequate understanding of integrin function in cutaneous wound healing and the wound microenvironment. Following cutaneous injury, keratinocytes migrate to restore the skin barrier, and macrophages aid in debris clearance. Thus, both keratinocytes and macrophages are critical to the coordination of tissue repair. Keratinocyte integrins have been shown to participate in this coordinated effort by regulating secreted factors, some of which crosstalk to distinct cells in the wound microenvironment. Epidermal integrin α3β1 is a receptor for laminin-332 in the cutaneous basement membrane. Here we show that wounds deficient in epidermal α3β1 express less epidermal-derived macrophage colony-stimulating factor 1 (CSF-1), the primary macrophage-stimulating growth factor. α3β1-deficient wounds also have fewer wound-proximal macrophages, suggesting that keratinocyte α3β1 may stimulate wound macrophages through the regulation of CSF-1. Indeed, using a set of immortalized keratinocytes, we demonstrate that keratinocyte-derived CSF-1 supports macrophage growth, and that α3β1 regulates <em>Csf1</em> expression through Src-dependent stimulation of Yes-associated protein (YAP)-Transcriptional enhanced associate domain (TEAD)-mediated transcription. Consistently, α3β1-deficient wounds <em>in vivo</em> display a substantially reduced number of keratinocytes with YAP-positive nuclei. Overall, our current findings identify a novel role for epidermal integrin α3β1 in regulating the cutaneous wound microenvironment by mediating paracrine crosstalk from keratinocytes to wound macrophages, implicating α3β1 as a potential target of wound therapy.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"127 ","pages":"Pages 48-56"},"PeriodicalIF":6.9,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716563","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":"Kidney resident macrophages have distinct subsets and multifunctional roles","authors":"Christine Chew ,&nbsp;Oliver J Brand ,&nbsp;Tomohiko Yamamura ,&nbsp;Craig Lawless ,&nbsp;Mychel Raony Paiva Teixeira Morais ,&nbsp;Leo Zeef ,&nbsp;I-Hsuan Lin ,&nbsp;Gareth Howell ,&nbsp;Sylvia Lui ,&nbsp;Franziska Lausecker ,&nbsp;Christopher Jagger ,&nbsp;Tovah N Shaw ,&nbsp;Siddharth Krishnan ,&nbsp;Flora A McClure ,&nbsp;Hayley Bridgeman ,&nbsp;Kelly Wemyss ,&nbsp;Joanne E Konkel ,&nbsp;Tracy Hussell ,&nbsp;Rachel Lennon","doi":"10.1016/j.matbio.2024.02.002","DOIUrl":"10.1016/j.matbio.2024.02.002","url":null,"abstract":"<div><h3>Background</h3><p>The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear.</p></div><div><h3>Methods</h3><p>Flow and imaging cytometry were used to determine the relative expression of CD81 and CX₃CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in <em>Cx3cr1</em>^CreER X <em>R26-yfp</em>-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and <em>Col4a5</em>^−/− (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses.</p></div><div><h3>Results</h3><p>In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX₃CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in <em>Col4a5^−/−</em> (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts.</p></div><div><h3>Conclusions</h3><p>We identified CD81 and CX₃CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"127 ","pages":"Pages 23-37"},"PeriodicalIF":6.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24000210/pdfft?md5=07a30ae5fc61894613edbbab00b8f6ca&pid=1-s2.0-S0945053X24000210-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708384","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":"Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss","authors":"Zhuoyue Chen ,&nbsp;Yaqing Huang ,&nbsp;Hao Xing ,&nbsp;Tiffany Tseng ,&nbsp;Hailey Edelman ,&nbsp;Rachel Perry ,&nbsp;Themis R. Kyriakides","doi":"10.1016/j.matbio.2024.02.001","DOIUrl":"10.1016/j.matbio.2024.02.001","url":null,"abstract":"<div><p>Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization of hydrogels derived from DEM prepared from WT or thrombospondin (TSP)-2 null muscle tissue. TSP2-null hydrogels, when compared to WT, displayed altered architecture, protein composition, and biomechanical properties and allowed enhanced invasion of C2C12 myocytes and chord formation by endothelial cells. They also displayed enhanced cell invasion, innervation, and angiogenesis following subcutaneous implantation. To evaluate their regenerative capacity, WT or TSP2 null hydrogels were used to treat VML injury to tibialis anterior muscles and the latter induced greater recruitment of repair cells, innervation, and blood vessel formation and reduced inflammation. Taken together, these observations indicate that TSP2-null hydrogels enhance angiogenesis and promote muscle repair in a VML model.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"127 ","pages":"Pages 38-47"},"PeriodicalIF":6.9,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690506","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":"Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung","authors":"Fengying Tang ,&nbsp;Stephen R. Reeves ,&nbsp;Jourdan E. Brune ,&nbsp;Mary Y. Chang ,&nbsp;Christina K. Chan ,&nbsp;Peter Waldron ,&nbsp;Sheona P. Drummond ,&nbsp;Caroline M. Milner ,&nbsp;Kimberly M. Alonge ,&nbsp;Stavros Garantziotis ,&nbsp;Anthony J. Day ,&nbsp;William A. Altemeier ,&nbsp;Charles W. Frevert","doi":"10.1016/j.matbio.2024.01.004","DOIUrl":"10.1016/j.matbio.2024.01.004","url":null,"abstract":"&lt;div&gt;&lt;p&gt;The inter-alpha-trypsin inhibitor (IαI) complex is composed of the bikunin core protein with a single chondroitin sulfate (CS) attached and one or two heavy chains (HCs) covalently linked to the CS chain. The HCs from IαI can be transferred to hyaluronan (HA) through a TNFα-stimulated gene-6 (TSG-6) dependent process to form an HC•HA matrix. Previous studies reported increased IαI, HA, and HC•HA complexes in mouse bronchoalveolar lavage fluid (BALF) post-influenza infection. However, the expression and incorporation of HCs into the HA matrix of the lungs during the clinical course of influenza A virus (IAV) infection and the biological significance of the HC•HA matrix are poorly understood. The present study aimed to better understand the composition of HC•HA matrices in mice infected with IAV and how these matrices regulate the host pulmonary immune response. In IAV infected mice bikunin, HC1–3, TSG-6, and HAS1–3 all show increased gene expression at various times during a 12-day clinical course. The increased accumulation of IαI and HA was confirmed in the lungs of infected mice using immunohistochemistry and quantitative digital pathology. Western blots confirmed increases in the IαI components in BALF and lung tissue at 6 days post-infection (dpi). Interestingly, HCs and bikunin recovered from BALF and plasma from mice 6 dpi with IAV, displayed differences in the HC composition by Western blot analysis and differences in bikunin's CS chain sulfation patterns by mass spectrometry analysis. This strongly suggests that the IαI components were synthesized in the lungs rather than translocated from the vascular compartment. HA was significantly increased in BALF at 6 dpi, and the HA recovered in BALF and lung tissues were modified with HCs indicating the presence of an HC•HA matrix. &lt;em&gt;In vitro&lt;/em&gt; experiments using polyinosinic-polycytidylic acid (poly(I:C)) treated mouse lung fibroblasts (MLF) showed that modification of HA with HCs increased cell-associated HA, and that this increase was due to the retention of HA in the MLF glycocalyx. &lt;em&gt;In vitro&lt;/em&gt; studies of leukocyte adhesion showed differential binding of lymphoid (Hut78), monocyte (U937), and neutrophil (dHL60) cell lines to HA and HC•HA matrices. Hut78 cells adhered to immobilized HA in a size and concentration-dependent manner. In contrast, the binding of dHL60 and U937 cells depended on generating a HC•HA matrix by MLF. Our &lt;em&gt;in vivo&lt;/em&gt; findings, using multiple bronchoalveolar lavages, correlated with our &lt;em&gt;in vitro&lt;/em&gt; findings in that lymphoid cells bound more tightly to the HA-glycocalyx in the lungs of influenza-infected mice than neutrophils and mononuclear phagocytes (MNPs). The neutrophils and MNPs were associated with a HC•HA matrix and were more readily lavaged from the lungs. In conclusion, this work shows increased IαI and HA accumulation and the formation of a HC•HA matrix in mouse lungs post-IAV infection. The formation of HA and HC•HA matrices could p","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"126 ","pages":"Pages 25-42"},"PeriodicalIF":6.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139474576","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":"Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFβ1/Smad3 signaling pathway","authors":"Run Zhao ,&nbsp;Jiale Dong ,&nbsp;Chunlei Liu ,&nbsp;Mingheng Li ,&nbsp;Ruiqian Tan ,&nbsp;Chengshuo Fei ,&nbsp;Yanlin Chen ,&nbsp;Xinxing Yang ,&nbsp;Jiawei Shi ,&nbsp;Jiajia Xu ,&nbsp;Liang Wang ,&nbsp;Peng Li ,&nbsp;Zhongmin Zhang","doi":"10.1016/j.matbio.2024.01.005","DOIUrl":"10.1016/j.matbio.2024.01.005","url":null,"abstract":"<div><p>Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical ligamentum flavum specimens. In laboratory experiments, it was demonstrated that THBS1 triggered the activation of Smad3 signaling induced by transforming growth factor β1 (TGFβ1), leading to the subsequent enhancement of COL1A2 and α-SMA, which are fibrosis markers. Furthermore, experiments conducted on a bipedal standing mouse model revealed that THBS1 played a crucial role in the development of LFH. Sestrin2 (SESN2) acted as a stress-responsive protein that suppressed the expression of THBS1, thus averting the progression of fibrosis in ligamentum flavum (LF) cells. To summarize, these results indicate that mechanical overloading causes an increase in THBS1 production, which triggers the TGFβ1/Smad3 signaling pathway and ultimately results in the development of LFH. Targeting the suppression of THBS1 expression may present a novel approach for the treatment of LFH.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"127 ","pages":"Pages 8-22"},"PeriodicalIF":6.9,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24000131/pdfft?md5=7bf72a3a078d6362ab463c417c0953c3&pid=1-s2.0-S0945053X24000131-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139571952","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":"Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy","authors":"Jeffrey Aalders ,&nbsp;Laurens Léger ,&nbsp;Louis Van der Meeren ,&nbsp;Sanjay Sinha ,&nbsp;Andre G. Skirtach ,&nbsp;Julie De Backer ,&nbsp;Jolanda van Hengel","doi":"10.1016/j.matbio.2024.01.003","DOIUrl":"10.1016/j.matbio.2024.01.003","url":null,"abstract":"<div><p>Pathogenic variants in the <span><em>FBN1</em></span><span> gene, which encodes the extracellular matrix protein<span> fibrillin-1, cause Marfan syndrome (MFS), which affects multiple organ systems, including the cardiovascular system. Myocardial dysfunction has been observed in a subset of patients with MFS and in several MFS mouse models. However, there is limited understanding of the intrinsic consequences of </span></span><em>FBN1</em><span> variants on cardiomyocytes (CMs). To elucidate the CM-specific contribution in Marfan's cardiomyopathy, cardiosphere cultures of CMs and cardiac fibroblasts (CFs) are used. CMs and CFs were derived by human induced pluripotent stem cell (iPSC) differentiation from MFS iPSCs with a pathogenic variant in </span><em>FBN1</em> (c.3725G&gt;<em>A</em>; p.Cys1242Tyr) and the corresponding CRISPR-corrected iPSC line (Cor).</p><p>Cardiospheres containing MFS CMs show decreased <span><em>FBN1, </em><em>COL1A2</em></span> and <span><em>GJA1</em></span><span> expression. MFS CMs cultured in cardiospheres have fewer binucleated CMs in comparison with Cor CMs. 13% of MFS CMs in cardiospheres are binucleated and 15% and 16% in cardiospheres that contain co-cultures with respectively MFS CFs and Cor CFs, compared to Cor CMs, that revealed up to 23% binucleation when co-cultured with CFs. The sarcomere length of CMs, as a marker of development, is significantly increased in MFS CMs interacting with Cor CF or MFS CF, as compared to monocultured MFS CMs. Nuclear blebbing was significantly more frequent in MFS CFs, which correlated with increased stiffness of the nuclear area compared to Cor CFs.</span></p><p>Our cardiosphere model for Marfan-related cardiomyopathy identified a contribution of CFs in Marfan-related cardiomyopathy and suggests that abnormal early development of CMs may play a role in the disease mechanism.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"126 ","pages":"Pages 14-24"},"PeriodicalIF":6.9,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139472567","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":"S100A4 a classical DAMP as a therapeutic target in fibrosis","authors":"Steven O'Reilly","doi":"10.1016/j.matbio.2024.01.002","DOIUrl":"10.1016/j.matbio.2024.01.002","url":null,"abstract":"<div><p>Fibrosis regardless of aetiology is characterised by persistently activated myofibroblasts that are contractile and secrete excessive amounts of extracellular matrix molecules that leads to loss of organ function. Damage-Associated Molecular Patterns (DAMPs) are endogenous host-derived molecules that are released from cells dying or under stress that can be triggered by a variety of insults, either chemical or physical, leading to an inflammatory response. Among these DAMPs is S100A4, part of the S100 family of calcium binding proteins that participate in a variety of cellular processes. S100A4 was first described in context of cancer as a pro-metastatic factor. It is now appreciated that aside from its role in cancer promotion, S100A4 is intimately involved in tissue fibrosis. The extracellular form of S100A4 exerts its effects through multiple receptors including Toll-Like Receptor 4 and RAGE to evoke signalling cascades involving downstream mediators facilitating extracellular matrix deposition and myofibroblast generation and can play a role in persistent activation of myofibroblasts. S100A4 may be best understood as an amplifier of inflammatory and fibrotic processes. S100A4 appears critical in systemic sclerosis pathogenesis and blocking the extracellular form of S100A4 in vivo in various animal models of disease mitigates fibrosis and may even reverse established disease. This review appraises S100A4’s position as a DAMP and its role in fibrotic conditions and highlight therapeutically targeting this protein to halt fibrosis, suggesting that it is a tractable target.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"127 ","pages":"Pages 1-7"},"PeriodicalIF":6.9,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458512","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}