Matrix Biology最新文献

{"title":"Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung","authors":"Fengying Tang , Stephen R. Reeves , Jourdan E. Brune , Mary Y. Chang , Christina K. Chan , Peter Waldron , Sheona P. Drummond , Caroline M. Milner , Kimberly M. Alonge , Stavros Garantziotis , Anthony J. Day , William A. Altemeier , Charles W. Frevert","doi":"10.1016/j.matbio.2024.01.004","DOIUrl":"10.1016/j.matbio.2024.01.004","url":null,"abstract":"<div><p>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. <em>In vitro</em> 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. <em>In vitro</em> 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 <em>in vivo</em> findings, using multiple bronchoalveolar lavages, correlated with our <em>in vitro</em> 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}

{"title":"Dynamic changes in mitral valve extracellular matrix, tissue mechanics and function in a mouse model of Marfan syndrome","authors":"Brittany A. Gonzalez ,&nbsp;Samuel W. Harmeyer ,&nbsp;Taejeong Song ,&nbsp;Sakthivel Sadayappan ,&nbsp;Katherine E. Yutzey","doi":"10.1016/j.matbio.2024.01.001","DOIUrl":"10.1016/j.matbio.2024.01.001","url":null,"abstract":"<div><h3>Objective</h3><p>Mouse models of Marfan syndrome (MFS) with <em>Fibrillin 1 (Fbn1)</em> variant C1041G exhibit cardiovascular abnormalities, including myxomatous valve disease (MVD) and aortic aneurism, with structural extracellular matrix (ECM) dysregulation. In this study, we examine the structure-function-mechanics relations of the mitral valve related to specific transitions in ECM composition and organization in progressive MVD in MFS mice from Postnatal day (P)7 to 1 year-of-age.</p></div><div><h3>Approach and results</h3><p>Mechanistic links between mechanical forces and biological changes in MVD progression were examined in <em>Fbn1^C1041G/+</em> MFS mice. By echocardiography, mitral valve dysfunction is prevalent at 2 months with a decrease in cardiac function at 6 months, followed by a preserved cardiac function at 12 months. Mitral valve (MV) regurgitation occurs in a subset of mice at 2–6 months, while progressive dilatation of the aorta occurs from 2 to 12 months. Mitral valve tissue mechanical assessments using a uniaxial Permeabilizable Fiber System demonstrate decreased stiffness of MFS MVs at all stages. Histological and microscopic analysis of ECM content, structure, and fiber orientation demonstrate that alterations in ECM mechanics, composition, and organization precede functional abnormalities in <em>Fbn1^C1041G/+</em>MFS MVs. At 2 months, ECM abnormalities are detected with an increase in proteoglycans and decreased stiffness of the mitral valve. By 6–12 months, collagen fiber remodeling is increased with abnormal fiber organization in MFS mitral valve leaflets. At the same time, matrifibrocyte gene expression characteristic of collagen-rich connective tissue is increased, as detected by RNA <em>in situ</em> hybridization and qPCR. Together, these studies demonstrate early prevalence of proteoglycans at 2 months followed by upregulation of collagen structure and organization with age in MVs of MFS mice.</p></div><div><h3>Conclusions</h3><p>Altogether, our data indicate dynamic regulation of mitral valve structure, tissue mechanics, and function that reflect changes in ECM composition, organization, and gene expression in progressive MVD. Notably, increased collagen fiber organization and orientation, potentially dependent on increased matrifibrocyte cell activity, is apparent with altered mitral valve mechanics and function in aging MFS mice.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"126 ","pages":"Pages 1-13"},"PeriodicalIF":6.9,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139102707","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":"A role for decorin in improving motor deficits after traumatic brain injury","authors":"Kaori Oshima ,&nbsp;Noah Siddiqui ,&nbsp;James E. Orfila ,&nbsp;Danelle Carter ,&nbsp;Justin Laing ,&nbsp;Xiaorui Han ,&nbsp;Igor Zakharevich ,&nbsp;Renato V Iozzo ,&nbsp;Arsen Ghasabyan ,&nbsp;Hunter Moore ,&nbsp;Fuming Zhang ,&nbsp;Robert J Linhardt ,&nbsp;Ernest E Moore ,&nbsp;Nidia Quillinan ,&nbsp;Eric P Schmidt ,&nbsp;Paco S Herson ,&nbsp;Joseph A Hippensteel","doi":"10.1016/j.matbio.2023.12.005","DOIUrl":"10.1016/j.matbio.2023.12.005","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is the leading cause of death and disability due to injury worldwide. Extracellular matrix (ECM) remodeling is known to significantly contribute to TBI pathophysiology. Glycosaminoglycans, which are long-chain, variably sulfated polysaccharides abundant within the ECM, have previously been shown to be substantially altered after TBI. In this study, we sought to delineate the dynamics of glycosaminoglycan alterations after TBI and discover the precise biologic processes responsible for observed glycosaminoglycan changes after injury. We performed state-of-the art mass spectrometry on brain tissues isolated from mice after TBI or craniotomy-alone. We observed dynamic changes in glycosaminoglycans at Day 1 and 7 post-TBI, with heparan sulfate, chondroitin sulfate, and hyaluronan remaining significantly increased after a week vis-à-vis craniotomy-alone tissues. We did not observe appreciable changes in circulating glycosaminoglycans in mice after experimental TBI compared to craniotomy-alone nor in patients with TBI and severe polytrauma compared to control patients with mild injuries, suggesting increases in injury site glycosaminoglycans are driven by local synthesis. We subsequently performed an unbiased whole genome transcriptomics analysis on mouse brain tissues 7 days post-TBI and discovered a significant induction of hyaluronan synthase 2, glypican-3, and decorin. The functional role of decorin after injury was further examined through multimodal behavioral testing comparing wild-type and <em>Dcn</em>^−/− mice. We discovered that genetic ablation of <em>Dcn</em> led to an overall negative effect of TBI on function, exacerbating motor impairments after TBI. Collectively, our results provide a spatiotemporal characterization of post-TBI glycosaminoglycan alterations in the brain ECM and support an important adaptive role for decorin upregulation after TBI.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"125 ","pages":"Pages 88-99"},"PeriodicalIF":6.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X23001282/pdfft?md5=d022f3ea7fe54f517f40a1bb507fa17f&pid=1-s2.0-S0945053X23001282-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138886419","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":"Tissue transglutaminase 2 has higher affinity for relaxed than for stretched fibronectin fibers","authors":"Kateryna Selcuk ,&nbsp;Alexander Leitner ,&nbsp;Lukas Braun ,&nbsp;Fanny Le Blanc ,&nbsp;Paulina Pacak ,&nbsp;Simon Pot ,&nbsp;Viola Vogel","doi":"10.1016/j.matbio.2023.12.006","DOIUrl":"10.1016/j.matbio.2023.12.006","url":null,"abstract":"<div><p>Tissue transglutaminase 2 (TG2) plays a vital role in stabilizing extracellular matrix (ECM) proteins through enzymatic crosslinking during tissue growth, repair, and inflammation. TG2 also binds non-covalently to fibronectin (FN), an essential component of the ECM, facilitating cell adhesion, migration, proliferation, and survival. However, the interaction between TG2 and fibrillar FN remains poorly understood, as most studies have focused on soluble or surface-adsorbed FN or FN fragments, which differ in their conformations from insoluble FN fibers. Using a well-established in vitro FN fiber stretch assay, we discovered that the binding of a crosslinking enzyme to ECM fibers is mechano-regulated. TG2 binding to FN is tuned by the mechanical tension of FN fibers, whereby TG2 predominantly co-localizes to low-tension FN fibers, while fiber stretching reduces their affinity for TG2. This mechano-regulated binding relies on the proximity between the N-terminal β-sandwich and C-terminal β-barrels of TG2. Crosslinking mass spectrometry (XL-MS) revealed a novel TG2-FN synergy site within TG2’s C-terminal β-barrels that interacts with FN regions located outside of the canonical gelatin binding domain, specifically FNI₂ and FNIII_14–15. Combining XL-MS distance restraints with molecular docking revealed the mechano-regulated binding mechanism between TG2 and modules FNI_7–9 by which mechanical forces regulate TG2-FN interactions. This highlights a previously unrecognized role of TG2 as a tension sensor for FN fibers. This novel interaction mechanism has significant implications in physiology and mechanobiology, including how forces regulate cell adhesion, spreading, migration, phenotype modulation, depending on the tensional state of ECM fibers. Data are available via ProteomeXchange with identifier PXD043976.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"125 ","pages":"Pages 113-132"},"PeriodicalIF":6.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X23001294/pdfft?md5=b6c1ae14ee1a8edd41da302bc438135e&pid=1-s2.0-S0945053X23001294-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138840941","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":"Inhibiting JAK1, not NF-κB, reverses the effect of pro-inflammatory cytokines on engineered human ligament function","authors":"Alec M. Avey ,&nbsp;Florence Devos ,&nbsp;Albany G. Roberts ,&nbsp;El Sayed El Essawy ,&nbsp;Keith Baar","doi":"10.1016/j.matbio.2023.12.007","DOIUrl":"10.1016/j.matbio.2023.12.007","url":null,"abstract":"<div><p>The role of inflammation in chronic tendon/ligament injury is hotly debated. There is less debate about inflammation following acute injury. To better understand the effect of acute inflammation, in this study we developed a multi-cytokine model of inflammatory tendinitis. The combined treatment with TNF-α, IL-1β, and IL-6, at dosages well below what are routinely used <em>in vitro</em>, decreased the mechanical properties and collagen content of engineered human ligaments. Treatment with this cytokine mixture resulted in an increase in phospho-NF-κB and MMP-1, did not affect procollagen production, and decreased STAT3 phosphorylation relative to controls. Using this more physiologically relevant model of acute inflammation, we inhibited NF-κB or JAK1 signaling in an attempt to reverse the negative effects of the cytokine mixture. Surprisingly, NF-κB inhibition led to an even greater decrease in mechanical function and collagen content. By contrast, inhibiting JAK1 led to an increase in mechanical properties, collagen content and thermal stability concomitant with a decrease in MMP-1. Our results suggest that inhibition of JAK1, not NF-κB, reverses the negative effects of pro-inflammatory cytokines on collagen content and mechanics in engineered human ligaments.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"125 ","pages":"Pages 100-112"},"PeriodicalIF":6.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X23001300/pdfft?md5=93ed043b25696febb73f4ac09bf0c956&pid=1-s2.0-S0945053X23001300-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139034614","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":"Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing","authors":"Jessica E. Ackerman ,&nbsp;Samantha N. Muscat ,&nbsp;Emmanuela Adjei-Sowah ,&nbsp;Antonion Korcari ,&nbsp;Anne E.C. Nichols ,&nbsp;Mark R. Buckley ,&nbsp;Alayna E. Loiselle","doi":"10.1016/j.matbio.2023.12.004","DOIUrl":"10.1016/j.matbio.2023.12.004","url":null,"abstract":"<div><p>Tendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target. While myofibroblasts are typically defined by the presence of αSMA+ stress fibers, αSMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of αSMA expression is not a translationally tenable approach. Recent work has demonstrated that Periostin-lineage (Postn^Lin) cells are a precursor for cardiac fibrosis-associated myofibroblasts. In contrast to this, here we show that Postn^Lin cells contribute to a transient αSMA+ myofibroblast population that is required for functional tendon healing, and that Periostin forms a supportive matrix niche that facilitates myofibroblast differentiation and persistence. Collectively, these data identify the Periostin matrix niche as a critical regulator of myofibroblast fate and persistence that could be targeted for therapeutic manipulation to facilitate regenerative tendon healing.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"125 ","pages":"Pages 59-72"},"PeriodicalIF":6.9,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X23001270/pdfft?md5=d1a0ad30e6274afc2d857c7e8bd9f04d&pid=1-s2.0-S0945053X23001270-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138635258","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":"Collagen prolyl 4-hydroxylase isoenzymes I and II have sequence specificity towards different X-Pro-Gly triplets","authors":"Antti M. Salo ,&nbsp;Pekka Rappu ,&nbsp;M．Kristian Koski ,&nbsp;Emma Karjalainen ,&nbsp;Valerio Izzi ,&nbsp;Kati Drushinin ,&nbsp;Ilkka Miinalainen ,&nbsp;Jarmo Käpylä ,&nbsp;Jyrki Heino ,&nbsp;Johanna Myllyharju","doi":"10.1016/j.matbio.2023.12.001","DOIUrl":"10.1016/j.matbio.2023.12.001","url":null,"abstract":"<div><p>Collagen biosynthesis requires several co- and post-translational modifications of lysine and proline residues to form structurally and functionally competent collagen molecules. Formation of 4-hydroxyproline (4Hyp) in Y-position prolines of the repetitive -X-Y-Gly- sequences provides thermal stability for the triple-helical collagen molecules. 4Hyp formation is catalyzed by a collagen prolyl 4-hydroxylase (C-P4H) family consisting of three isoenzymes. Here we identify specific roles for the two main C-P4H isoenzymes in collagen hydroxylation by a detailed 4Hyp analysis of type I and IV collagens derived from cell and tissue samples. Loss of C-P4H-I results in underhydroxylation of collagen where the affected prolines are not uniformly distributed, but mainly present in sites where the adjacent X-position amino acid has a positively charged or a polar uncharged side chain. In contrast, loss of C-P4H-II results in underhydroxylation of triplets where the X-position is occupied by a negatively charged amino acid glutamate or aspartate. Hydroxylation of these triplets was found to be important as loss of C-P4H-II alone resulted in reduced collagen melting temperature and altered assembly of collagen fibrils and basement membrane. The observed C-P4H isoenzyme differences in substrate specificity were explained by selective binding of the substrate to the active site resulting in distinct differences in Km and Vmax values. Furthermore, our results clearly show that the substrate proline selection is not dependent on the collagen type, but the main determinant is the X-position amino acid of the -X-Pro-Gly- triplet. Although our data clearly shows the necessity of both C-P4H-I and II for normal prolyl 4-hydroxylation and function of collagens, the mRNA expression of the isoenzymes with various procollagens was, surprisingly, not tightly coordinated, suggesting additional levels of control. In conclusion, this study provides a molecular level explanation for the need of multiple C-P4H isoenzymes to generate collagen molecules capable to assemble into intact extracellular matrix structures.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"125 ","pages":"Pages 73-87"},"PeriodicalIF":6.9,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X23001245/pdfft?md5=5624e861c2d6994e568ea89d4782bb0e&pid=1-s2.0-S0945053X23001245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138578278","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}