Matrix Biology Plus最新文献

{"title":"Analysis of cancer cell line and tissue RNA sequencing data reveals an essential and dark matrisome","authors":"Joshua A. Rich ,&nbsp;Yu Fan ,&nbsp;Qingrong Chen ,&nbsp;Daoud Meerzaman ,&nbsp;William G. Stetler-Stevenson ,&nbsp;David Peeney","doi":"10.1016/j.mbplus.2024.100156","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100156","url":null,"abstract":"<div><p>Extracellular matrix remodeling is a hallmark of tissue development, homeostasis, and disease. The processes that mediate remodeling, and the consequences of such, are the topic of extensive focus in biomedical research. Cell culture methods represent a crucial tool utilized by those interested in matrisome function, the easiest of which are implemented with immortalized/cancer cell lines. These cell lines often form the foundations of a research proposal, or serve as vehicles of validation for other model systems. For these reasons, it is important to understand the complement of matrisome genes that are expressed when identifying appropriate cell culture models for hypothesis testing. To this end, we harvested bulk RNA sequencing data from the Cancer Cell Line Encyclopedia (CCLE) to assess matrisome gene expression in 1019 human cell lines. Our examination reveals that a large proportion of the matrisome is poorly represented in human cancer cell lines, with approximately 10% not expressed above threshold in any of the cell lines assayed. Conversely, we identify clusters of essential/common matrisome genes that are abundantly expressed in cell lines. To validate these observations against tissue data, we compared our findings with bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) portal and The Cancer Genome Atlas (TCGA) program. This comparison demonstrates general agreement between the “essential/common” and “dark/uncommon” matrisome across the three datasets, albeit with discordance observed in 59 matrisome genes between cell lines and tissues. Notably, all of the discordant genes are essential/common in tissues yet minimally expressed in cell lines, underscoring critical considerations for matrix biology researchers employing immortalized cell lines for their investigations.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000164/pdfft?md5=243092e6a458f09effb7c337f5b72353&pid=1-s2.0-S2590028524000164-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of the extracellular matrix in the human adrenal cortex","authors":"Jean Lucas Kremer ,&nbsp;Henrique Sanchez Ortega ,&nbsp;Talita Souza-Siqueira ,&nbsp;Claudia Blanes Angeli ,&nbsp;Leo Kei Iwai ,&nbsp;Giuseppe Palmisano ,&nbsp;Claudimara Ferini Pacicco Lotfi","doi":"10.1016/j.mbplus.2024.100158","DOIUrl":"10.1016/j.mbplus.2024.100158","url":null,"abstract":"<div><p>The extracellular matrix (ECM) comprises macromolecules that shape a complex three-dimensional network. Filling the intercellular space and playing a crucial role in the structure and function of tissues, ECM regulates essential cellular processes such as adhesion, differentiation, and cell signaling. In the human adrenal gland, composed of cortex and medulla surrounded by a capsule, the ECM has not yet been directly described, although its impact on the processes of proliferation and steroidogenesis of the adrenal cortex is recognized. This study analyzes the ECM of the adult human adrenal cortex, which was separated into outer fraction (OF) and inner fraction (IF), by comparing their proteomic profiles. The study discusses the composition, spatial distribution, and relevance of differentially expressed ECM signatures of the adrenal cortex matrisome on adrenal structure and function. The findings were validated through database analysis (cross-validation), histochemical, and immunohistochemical approaches. A total of 121 ECM proteins were identified and categorized into glycoproteins, collagens, ECM regulators, proteoglycans, ECM-affiliated proteins, and secreted factors. Thirty-one ECM proteins were identified only in OF, nine only in IF, and 81 were identified in common with both fractions. Additionally, 106 ECM proteins were reported in the Human matrisome DB 2.0, and the proteins differentially expressed in OF and IF, were identified. This study provides significant insights into the composition and regulation of the ECM in the human adrenal cortex, shedding light on the adrenal microenvironment and its role in the functioning, maintenance, and renewal of the adrenal gland.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000188/pdfft?md5=cfc1b36c2953d4b9d1fcbeb6a6166497&pid=1-s2.0-S2590028524000188-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartilage-derived cells display heterogeneous pericellular matrix synthesis in agarose microgels","authors":"Marloes van Mourik ,&nbsp;Bart M. Tiemeijer ,&nbsp;Maarten van Zon ,&nbsp;Florencia Abinzano ,&nbsp;Jurjen Tel ,&nbsp;Jasper Foolen ,&nbsp;Keita Ito","doi":"10.1016/j.mbplus.2024.100157","DOIUrl":"10.1016/j.mbplus.2024.100157","url":null,"abstract":"<div><p>The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-β1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-β1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000176/pdfft?md5=a6314ad1e2b54f25ca6e30f6af88488b&pid=1-s2.0-S2590028524000176-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saturated fatty acids negatively affect musculoskeletal tissues in vitro and in vivo","authors":"Ryan T. Lin ,&nbsp;Benjamin Osipov ,&nbsp;Danielle Steffen ,&nbsp;Marin Chamberlin ,&nbsp;Suraj J. Pathak ,&nbsp;Blaine A. Christiansen ,&nbsp;Kevin J.M. Paulussen ,&nbsp;Keith Baar","doi":"10.1016/j.mbplus.2024.100153","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100153","url":null,"abstract":"<div><p>Fish oils rank among the world’s most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on <em>in vitro</em>-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an <em>in vitro</em> artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis <em>in vitro</em> to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both <em>in vitro</em> and <em>in vivo</em>.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000139/pdfft?md5=d180d21910ede72698b66b840b4bdb9a&pid=1-s2.0-S2590028524000139-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomaterial systems for evaluating the influence of ECM mechanics on anti-fibrotic therapeutic efficacy","authors":"Aryssa Simpson ,&nbsp;Emily P. Mihalko ,&nbsp;Caroline Fox ,&nbsp;Smriti Sridharan ,&nbsp;Manasi Krishnakumar ,&nbsp;Ashley C. Brown","doi":"10.1016/j.mbplus.2024.100150","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100150","url":null,"abstract":"<div><p>Cardiac fibrosis is characterized by excessive accumulation and deposition of ECM proteins. Cardiac fibrosis is commonly implicated in a variety of cardiovascular diseases, including post-myocardial infarction (MI). We have previously developed a dual-delivery nanogel therapeutic to deliver tissue plasminogen activator (tPA) and Y-27632 (a ROCK inhibitor) to address MI-associated coronary artery occlusion and downregulate cell-contractility mediated fibrotic responses. Initial <em>in vitro</em> studies were conducted on glass substrates. The study presented here employs the use of polyacrylamide (PA) gels and microgel thin films to mimic healthy and fibrotic cardiac tissue mechanics. Soft and stiff polyacrylamide substrates or high and low loss tangent microgel thin films were utilized to examine the influence of cell-substrate interactions on dual-loaded nanogel therapeutic efficacy. In the presence of Y-27632 containing nanogels, a reduction of fibrotic marker expression was noted on traditional PA gels mimicking healthy and fibrotic cardiac tissue mechanics. These findings differed on more physiologically relevant microgel thin films, where early treatment with the ROCK inhibitor intensified the fibrotic related responses.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000103/pdfft?md5=26ed3c5a9d143d43ca9d30c905a890a9&pid=1-s2.0-S2590028524000103-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141242854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topographic modification of the extracellular matrix precedes the onset of bladder cancer","authors":"Chiara Venegoni ,&nbsp;Filippo Pederzoli ,&nbsp;Irene Locatelli ,&nbsp;Elisa Alchera ,&nbsp;Laura Martinez-Vidal ,&nbsp;Alessia Di Coste ,&nbsp;Marco Bandini ,&nbsp;Andrea Necchi ,&nbsp;Francesco Montorsi ,&nbsp;Andrea Salonia ,&nbsp;Marco Moschini ,&nbsp;Jithin Jose ,&nbsp;Federico Scarfò ,&nbsp;Roberta Lucianò ,&nbsp;Massimo Alfano","doi":"10.1016/j.mbplus.2024.100154","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100154","url":null,"abstract":"<div><h3>Background</h3><p>Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment.</p></div><div><h3>Objective</h3><p>Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to <em>bona fide</em> tumor) and whether those changes favour the development of NMIBC.</p></div><div><h3>Design, Setting, and Participants</h3><p>Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC.</p></div><div><h3>Findings</h3><p>Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor.</p></div><div><h3>Conclusions</h3><p>The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000140/pdfft?md5=2079258384fc3673f0b391044829eb0e&pid=1-s2.0-S2590028524000140-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141244822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrisome proteomics reveals novel mediators of muscle remodeling with aerobic exercise training","authors":"Pattarawan Pattamaprapanont ,&nbsp;Eileen M. Cooney ,&nbsp;Tara L. MacDonald ,&nbsp;Joao A. Paulo ,&nbsp;Hui Pan ,&nbsp;Jonathan M. Dreyfuss ,&nbsp;Sarah J. Lessard","doi":"10.1016/j.mbplus.2024.100159","DOIUrl":"10.1016/j.mbplus.2024.100159","url":null,"abstract":"<div><p>Skeletal muscle has a unique ability to remodel in response to stimuli such as contraction and aerobic exercise training. Phenotypic changes in muscle that occur with training such as a switch to a more oxidative fiber type, and increased capillary density contribute to the well-known health benefits of aerobic exercise. The muscle matrisome likely plays an important role in muscle remodeling with exercise. However, due to technical limitations in studying muscle ECM proteins, which are highly insoluble, little is known about the muscle matrisome and how it contributes to muscle remodeling. Here, we utilized two-fraction methodology to extract muscle proteins, combined with multiplexed tandem mass tag proteomic technology to identify 161 unique ECM proteins in mouse skeletal muscle. In addition, we demonstrate that aerobic exercise training induces remodeling of a significant proportion of the muscle matrisome. We performed follow-up experiments to validate exercise-regulated ECM targets in a separate cohort of mice using Western blotting and immunofluorescence imaging. Our data demonstrate that changes in several key ECM targets are strongly associated with muscle remodeling processes such as increased capillary density in mice. We also identify LOXL1 as a novel muscle ECM target associated with aerobic capacity in humans. In addition, publically available data and databases were used for in silico modeling to determine the likely cellular sources of exercise-induced ECM remodeling targets and identify ECM interaction networks. This work greatly enhances our understanding of ECM content and function in skeletal muscle and demonstrates an important role for ECM remodeling in the adaptive response to exercise. The raw MS data have been deposited to the ProteomeXchange with identifier PXD053003.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259002852400019X/pdfft?md5=f9ac69cc862df261d53366122e2ba4fa&pid=1-s2.0-S259002852400019X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue material properties, whole-bone morphology and mechanical behavior in the Fbn1C1041G/+ mouse model of Marfan syndrome","authors":"Elizabeth A. Zimmermann ,&nbsp;Taylor DeVet ,&nbsp;Myriam Cilla ,&nbsp;Laia Albiol ,&nbsp;Kyle Kavaseri ,&nbsp;Christine Andrea ,&nbsp;Catherine Julien ,&nbsp;Kerstin Tiedemann ,&nbsp;Arash Panahifar ,&nbsp;Sima A. Alidokht ,&nbsp;Richard Chromik ,&nbsp;Svetlana V. Komarova ,&nbsp;Dieter P. Reinhardt ,&nbsp;Paul Zaslansky ,&nbsp;Bettina M. Willie","doi":"10.1016/j.mbplus.2024.100155","DOIUrl":"10.1016/j.mbplus.2024.100155","url":null,"abstract":"<div><p>Marfan syndrome (MFS) is a connective tissue disorder caused by pathogenic mutations in FBN1. In bone, the protein fibrillin-1 is found in the extracellular matrix where it provides structural support of elastic fiber formation, stability for basement membrane, and regulates the bioavailability of growth factors. Individuals with MFS exhibit a range of skeletal complications including low bone mineral density and long bone overgrowth. However, it remains unknown if the bone phenotype is caused by alteration of fibrillin-1′s structural function or distortion of its interactions with bone cells. To assess the structural effects of the fibrillin-1 mutation, we characterized bone curvature, microarchitecture, composition, porosity, and mechanical behavior in the <em>Fbn1</em>^C1041G/+ mouse model of MFS. Tibiae of 10, 26, and 52-week-old female <em>Fbn1</em>^C1041G/+ and littermate control (LC) mice were analyzed. Mechanical behavior was assessed via in vivo strain gauging, finite element analysis, <em>ex vivo</em> three-point bending, and nanoindentation. Tibial bone morphology and curvature were assessed with micro computed tomography (μCT). Bone composition was measured with Fourier transform infrared (FTIR) imaging. Vascular and osteocyte lacunar porosity were assessed by synchrotron computed tomography. <em>Fbn1</em>^C1041G/+ mice exhibited long bone overgrowth and osteopenia consistent with the MFS phenotype. Trabecular thickness was lower in <em>Fbn1</em>^C1041G/+ mice but cortical bone microarchitecture was similar in <em>Fbn1</em>^C1041G/+ and LC mice. Whole bone curvature was straighter below the tibio-fibular junction in the medial–lateral direction and more curved above in LC compared to <em>Fbn1</em>^C1041G/+ mice. The bone matrix crystallinity was 4 % lower in <em>Fbn1</em>^C1041G/+ mice compared to LC, implying that mineral platelets in LCs have greater crystal size and perfection than <em>Fbn1</em>^C1041G/+ mice. Structural and mechanical properties were similar between genotypes. Cortical diaphyseal lacunar porosity was lower in <em>Fbn1</em>^C1041G/+ mice compared to LC; this was a result of the average volume of an individual osteocyte lacunae being smaller. These data provide valuable insights into the bone phenotype and its contribution to fracture risk in this commonly used mouse model of MFS.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000152/pdfft?md5=aa5b85d8cec6470f016ad8dea315109f&pid=1-s2.0-S2590028524000152-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation","authors":"Mikala C. Mueller ,&nbsp;Yanmei Du ,&nbsp;Lori A. Walker ,&nbsp;Chelsea M. Magin","doi":"10.1016/j.mbplus.2024.100145","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100145","url":null,"abstract":"<div><p>Respiratory diseases like pulmonary arterial hypertension (PAH) frequently exhibit sexual dimorphism. Female PAH patients are more susceptible to the disease but have increased survival rates. This phenomenon is known as the estrogen paradox, and the underlying mechanisms are not fully understood. During PAH progression in vivo, human pulmonary arterial adventitial fibroblasts (hPAAFs) differentiate into an activated phenotype. These cells produce excess, aberrant extracellular matrix proteins that stiffen the surrounding pulmonary arterial tissues. Here, we employed dynamic poly(ethylene glycol)-alpha methacrylate (PEGαMA)-based biomaterials to study how the age and sex of human serum influenced hPAAF activation in response to microenvironmental stiffening <em>in vitro</em>. Results showed female and male cells responded differently to increases in microenvironmental stiffness and serum composition. Male hPAAFs were less activated than female cells on soft hydrogels and more responsive to increases in microenvironmental stiffness regardless of serum composition. Female hPAAF activation followed this pattern only when cultured in younger (age &lt; 50) female serum or when older (age ≥ 50) female serum was supplemented with estradiol. Otherwise, female hPAAF activation was relatively high on both soft and stiffened hydrogels, with little difference in activation between the two conditions. Collectively, these results suggest that it may be possible to model the estrogen paradox observed in PAH <em>in vitro</em> and that it is critical for researchers to report cell sex and serum source when conducting <em>in vitro</em> experimentation.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"22 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259002852400005X/pdfft?md5=deec13ac5f0ad7be215c527f23382d18&pid=1-s2.0-S259002852400005X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laminin-derived peptide, IKVAV, modulates macrophage phenotype through integrin mediation","authors":"Aakanksha Jha ,&nbsp;Erika Moore","doi":"10.1016/j.mbplus.2024.100143","DOIUrl":"10.1016/j.mbplus.2024.100143","url":null,"abstract":"<div><p>Macrophages are highly plastic immune cells known to exist on a spectrum of phenotypes including pro-inflammatory (M1) or pro-healing (M2). Macrophages interact with extracellular matrix (ECM) ligands, such as fragments of collagen and laminin. Interaction of macrophages with ECM ligands is mediated through integrin receptors. However, the role of ECM ligands in directing macrophage function through integrins is not yet fully understood. Particularly, α2β1 has been implicated in modulating macrophage function, but complexity in mechanisms employed for integrin-ligation especially with laminin-derived peptides makes it challenging to understand macrophage-ECM interactions. We hypothesize that targeting α2β1 through laminin-derived peptide, IKVAV, will modulate macrophage phenotype. In this work we: i) investigated macrophage response to IKVAV in 2D and in a 3D platform, and ii) identified α2β1′s role as it pertains to macrophage modulation via IKVAV. Soluble IKVAV treatment significantly reduced M1 markers and increased M2 markers via immunocytochemistry and gene expression. While the 3D ECM-mimicking PEG-IKVAV hydrogels did not have significant effects in modulating macrophage phenotype, we found that macrophage modulation via IKVAV is dependent on the concentration of peptide used and duration of exposure. To investigate integrin-ligand interactions for macrophages, α2β1 signaling was modulated by antagonists and agonists. We observed that blocking α2β1 reduces M1 activation. To understand integrin-ligand interactions and leveraging the therapeutic ability of macrophages in designing immunomodulatory solutions, it is critical to elucidate IKVAV’s role in mediating macrophage phenotype.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"22 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000036/pdfft?md5=9fc044be5e1e4dc4a1f095bb96b9b049&pid=1-s2.0-S2590028524000036-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139882274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}