Matrix Biology Plus最新文献

{"title":"Small Integrin binding Ligand N-linked Glycoproteins, prostate-specific antigen and time to prostate cancer diagnosis","authors":"Alka Jain ,&nbsp;Ying Ni ,&nbsp;Daisy Zhang ,&nbsp;Eleanor M. Simonsick ,&nbsp;E. Jeffrey Metter ,&nbsp;Kalu U. Ogbureke ,&nbsp;Larry W. Fisher ,&nbsp;Neal S. Fedarko","doi":"10.1016/j.mbplus.2025.100171","DOIUrl":"10.1016/j.mbplus.2025.100171","url":null,"abstract":"<div><div>Background: <u>S</u>mall <u>I</u>ntegrin <u>B</u>inding <u>Li</u>gand <u>N</u>-linked <u>G</u>lycoproteins (SIBLINGs¹) were associated with cancer in cross-sectional studies. Whether SIBLINGs associate with preclinical disease is unknown. Methods: A retrospective longitudinal case control study was performed to determine the association of SIBLINGs and prostate-specific antigen (PSA) with preclinical disease. Paired serum samples from 109 cancer-free Baltimore Longitudinal Study on Aging participants were divided into those that were either most distal or proximal to diagnosis (cases) or censored (controls). Dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), osteopontin (OPN), and PSA were measured by immunoassay and dichotomized into low or high based on their respective cut-off values. Associations of time to diagnosis or death, modeled as disease-free survival (DFS) or overall survival (OS), were assessed using Kaplan Meier and Cox proportional hazard survival estimates on individual and aggregated biomarkers in distal or proximal sets separately. Models were adjusted for relevant covariates. A false discovery rate analysis assessed significance of hazard ratios (HRs) in sets. Results: Biomarkers/aggregates identified as true discoveries for DFS included DSPP + PSA, OPN + PSA, DSPP + BSP + PSA, DSPP + OPN + PSA, where unadjusted distal HRs ranged between 11 and 27 and after adjusting for age from 7 to 15, while proximal HRs ranged between 6 and 10 unadjusted and 5 to 12 after adjusting for age. For proximal OS, true discoveries included DSPP + BSP, DSPP + OPN, DSPP + BSP + OPN, and DSPP + OPN + PSA where unadjusted HRs ranged between 6 and 20 while age-adjusted HRs ranged between 5 and 12. Conclusions: These observations support SIBLINGs as biomarkers that associate with DFS and OS in prediagnosis samples.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715291","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":"Crosstalk between T cells and fibroblasts in biomaterial-mediated fibrosis","authors":"Mathew Kibet,&nbsp;Daniel Abebayehu","doi":"10.1016/j.mbplus.2025.100172","DOIUrl":"10.1016/j.mbplus.2025.100172","url":null,"abstract":"<div><div>Biomaterial implants are a critical aspect of our medical therapies and biomedical research and come in various forms: stents, implantable glucose sensors, orthopedic implants, silicone implants, drug delivery systems, and tissue engineered scaffolds. Their implantation triggers a series of biological responses that often times lead to the foreign body response and subsequent fibrotic encapsulation, a dense ECM-rich capsule that isolates the biomaterial and renders it ineffective. These responses lead to the failure of biomaterials and is a major hurdle to overcome and in promoting their success. Much attention has been given to macrophage populations for the inflammatory component of these responses to biomaterials but recent work has identified an important role of T cells and their ability to modulate fibroblast activity and vice versa. In this review, we focus on T cell-fibroblast crosstalk by exploring T cell subsets, critical signaling pathways, and fibroblast populations that have been shown to dictate biomaterial-mediated fibrosis. We then highlight emerging technologies and model systems that enable new insights and avenues to T cell-fibroblast crosstalk that will improve biomaterial outcomes.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100172"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703907","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":"Development of an in vitro platform for epithelial-stromal interactions: A basement membrane-containing scaffold from decellularized porcine bladders","authors":"J.A. Ramirez ,&nbsp;S. Estrada ,&nbsp;M.C. Harmsen ,&nbsp;P.K. Sharma","doi":"10.1016/j.mbplus.2025.100169","DOIUrl":"10.1016/j.mbplus.2025.100169","url":null,"abstract":"<div><div>The first organized extracellular matrix that appears during mammalian embryogenesis is a basement membrane (BM), BM is present in all adult epithelia, endothelia, muscle, nerve and fat tissues. BM is a sub-micrometer thick compact lattice of macromolecules that is maintained by the adhered cells. Systems such as collagen gels, Matrigel® or synthetic polymeric scaffolds have been proposed to mimic the BM and to study the interactions between different cell types, but all lack a structured BM. Here we aimed to obtain and characterize a natural, thin basement membrane-containing scaffold from pig urinary bladders that are subjected to blunt dissection of layers and decellularization steps, preserving the near native BM with a few layers of underlying connective tissue to maintain its structural integrity. The scanning electron microscopy, confocal multiphoton microscopy and immunohistochemistry helped confirm the presence of the BM. A veil-like network composed of thin fibers was present on top of a course network, and glycosaminoglycans, collagen and basement membrane proteins were present. The scaffold’s ability to repopulation and basement membrane barrier function were further confirmed when HaCaT and MRC5 cells attached and remained respectively on the epithelial and mesenchymal side without any crossover. Cells remained viable till 2 weeks. This BM-containing scaffold allows to create <em>in vitro</em> models of epithelial-mesenchymal tissues through a structured basement membrane and investigate basement membrane dynamics. The basement membrane-containing scaffold was found to be isotropic under uniaxial tension with a failure strain of 0.25 allowing its use to investigate strain induced basement membrane dynamics.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552126","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 changing extracellular matrix stiffness drives Schwann cell phenotype","authors":"Alyssa Montgomery ,&nbsp;Jennifer Westphal ,&nbsp;Andrew E. Bryan ,&nbsp;Greg M. Harris","doi":"10.1016/j.mbplus.2024.100167","DOIUrl":"10.1016/j.mbplus.2024.100167","url":null,"abstract":"<div><div>Schwann cells (SCs) hold key roles in axonal function and maintenance in the peripheral nervous system (PNS) and are a critical component to the regeneration process following trauma. Following PNS trauma, SCs respond to both physical and chemical signals to modify phenotype and assist in the regeneration of damaged axons and extracellular matrix (ECM). There is currently a lack of knowledge regarding the SC response to dynamic, temporal changes in the ECM brought on by swelling and the development of scar tissue as part of the body’s wound-healing process. Thus, this work seeks to utilize a biocompatible, mechanically tunable biomaterial to mimic changes in the microenvironment following injury and over time. Previously, we have reported that ECM cues such as ligand type and substrate stiffness impact SC phenotype and plasticity, which was demonstrated by SCs on mechanically stable biomaterials. However, to better realize SC potential for plasticity following traumatic injury, a UV-tunable polydimethylsiloxane (PDMS) substrate with dynamically changing stiffness was utilized to mimic changes over time in the microenvironment. The dynamic biomaterial showed an increase in stress fibers, greater YAP expression, and fluctuations in c-Jun production in SCs in comparison to stiff and soft static controls. Utilizing biomaterials to better understand the role between temporal mechanical dynamics and SC phenotype holds a very high potential for developing future PNS therapies.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"25 ","pages":"Article 100167"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048548","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":"Loss of Cochlin drives impairments in tendon structure and function","authors":"Emmanuela Adjei-Sowah ,&nbsp;Elsa Lecaj ,&nbsp;Neeta Adhikari ,&nbsp;Clara Sensini ,&nbsp;Anne E.C. Nichols ,&nbsp;Mark R. Buckley ,&nbsp;Alayna E. Loiselle","doi":"10.1016/j.mbplus.2025.100168","DOIUrl":"10.1016/j.mbplus.2025.100168","url":null,"abstract":"<div><div>Aging tendons undergo disruptions in homeostasis, increased susceptibility to injury, and reduced capacity for healing. Exploring the mechanisms behind this disruption in homeostasis is essential for developing therapeutics aimed at maintaining tendon health through the lifespan. We have previously identified that the extracellular matrix protein, <em>Cochlin</em>, which is highly expressed in healthy flexor tendon, is consistently lost during both natural aging and upon depletion of Scleraxis-lineage cells in young animals, which recapitulates many aging-associated homeostatic disruptions. Therefore, we examined the effects of <em>Cochlin^-/-</em> on tendon maturation and hypothesized that loss of Cochlin would disrupt normal tendon maturation and recapitulate phenotypes associated with disrupted adult tendon homeostasis, including alterations in collagen fibril organization, and impaired tendon mechanics. By 3-months of age, <em>Cochlin^-/-</em> flexor tendons exhibited altered collagen structure, with these changes persisting through at least 9-months. In addition, Cochlin<em>^-/-</em> tendons demonstrated significant declines in structural and material properties at 6-months, and structural properties at 9-months. While <em>Cochlin^-/-</em> did not drastically change the overall tendon proteome, consistent decreases in proteins associated with RNA metabolism, extracellular matrix production and the cytoskeleton were observed in <em>Cochlin</em>^-/-. Interestingly, disrupted tendon maturation via <em>Cochlin^-/-</em> did not impair the tendon healing process. Taken together, these data define a critical role for Cochlin in facilitating physiological tendon maturation.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"25 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478552","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":"Investigation of neuro-regenerative therapeutic potential of nerve composite matrix hydrogels embedded with adipose-derived stem cells","authors":"Inha Baek,&nbsp;Younghye Song","doi":"10.1016/j.mbplus.2024.100165","DOIUrl":"10.1016/j.mbplus.2024.100165","url":null,"abstract":"<div><div>Traumatic spinal cord injury (SCI) induces permanent sensorimotor deficit below the site of injury. There is various research conducted to provide effective therapy, however, SCI is still considered incurable due to the complex nature of the injury site. Recently, our lab developed a combinatorial therapeutic for SCI repair comprising human adipose-derived stem cell (hASC)-embedded nerve composite hydrogels using different ratios of decellularized sciatic nerve (dSN) and spinal cord (dSC) matrices. This study investigated angiogenic and neurotrophic effects of the combinatorial therapeutic in vitro. Compression testing was performed to analyze mechanical properties of the composite hydrogels and showed no significant difference between all hydrogel groups. Next, pro-angiogenic factors and neurotrophins secreted from hASCs within different ratios of the composite hydrogels were analyzed and we found culture durations and extracellular matrix (ECM) composition affect secretory behavior. Interestingly, ECM compositional difference between hydrogel groups had little influence on human brain microvascular endothelial cells (HBVECs) infiltration and dorsal root ganglia (DRG) neurite outgrowth. Finally, we conducted proteomic analysis to identify the ECM components potentially contributing to these observed effects. Taken together, dSN:dSC = 1:2 hydrogel showed slightly better therapeutic potentials, warranting validation using <em>in vivo</em> studies.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704009","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":"A human stem cell-derived model reveals pathologic extracellular matrix remodeling in diabetic podocyte injury","authors":"Yasmin Roye ,&nbsp;Carmen Miller ,&nbsp;Titilola D. Kalejaiye ,&nbsp;Samira Musah","doi":"10.1016/j.mbplus.2024.100164","DOIUrl":"10.1016/j.mbplus.2024.100164","url":null,"abstract":"<div><div>Diabetic nephropathy results from chronic (or uncontrolled) hyperglycemia and is the leading cause of kidney failure. The kidney’s glomerular podocytes are highly susceptible to diabetic injury and subsequent non-reversible degeneration. We generated a human induced pluripotent stem (iPS) cell-derived model of diabetic podocytopathy to investigate disease pathogenesis and progression. The model recapitulated hallmarks of podocytopathy that precede proteinuria including retraction of foot processes and podocytopenia (detachment from the extracellular matrix (ECM)). Moreover, hyperglycemia-induced injury to podocytes exacerbated remodeling of the ECM. Specifically, mature podocytes aberrantly increased expression and excessively deposited collagen (IV)α1α1α2 that is normally abundant in the embryonic glomerulus. This collagen (IV) imbalance coincided with dysregulation of lineage-specific proteins, structural abnormalities of the ECM, and podocytopenia – a mechanism not shared with endothelium and is distinct from drug-induced injury. Intriguingly, repopulation of hyperglycemia-injured podocytes on decellularized ECM scaffolds isolated from healthy podocytes attenuated the loss of synaptopodin (a mechanosensitive protein associated with podocyte health). These results demonstrate that human iPS cell-derived podocytes can facilitate <em>in vitro</em> studies to uncover the mechanisms of chronic hyperglycemia and ECM remodeling and guide disease target identification.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100164"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663609","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":"Bone quality relies on hyaluronan synthesis – Insights from mice with complete knockout of hyaluronan synthase expression","authors":"A. Saalbach ,&nbsp;M. Stein ,&nbsp;S. Lee ,&nbsp;U. Krügel ,&nbsp;M. Haffner-Luntzer ,&nbsp;K. Krohn ,&nbsp;S. Franz ,&nbsp;J.C. Simon ,&nbsp;J. Tuckermann ,&nbsp;U. Anderegg","doi":"10.1016/j.mbplus.2024.100163","DOIUrl":"10.1016/j.mbplus.2024.100163","url":null,"abstract":"<div><div>Bone consists of a complex mineralised matrix that is maintained by a controlled equilibrium of synthesis and resorption by different cell types. Hyaluronan (HA) is an important glycosaminoglycan in many tissues including bone.</div><div>Previously, the importance of HA synthesis for bone development during embryogenesis has been shown. We therefore investigated whether HA synthesis is involved in adult bone turnover and whether abrogation of HA synthesis in adult mice would alter bone quality.</div><div>To achieve complete abrogation of HA synthesis in adult mice, we generated a novel Has-total knockout (Has-tKO) mouse model in which a constitutive knockout of Has1 and Has3 was combined with an inducible, Ubc-Cre-driven Has2 knockout.</div><div>By comparing bone tissue from wild-type, Has1,3 double knockout and Has-tKO mice, we demonstrate that Has2-derived HA mainly contributes to the HA content in bone. Furthermore, Has-tKO mice show a significant decrease of bone integrity in trabecular and cortical bone, as shown by µ-CT analysis. These effects are detectable as early as five weeks after induced Has2 deletion, irrespective of sex and progress with age.</div><div>Mesenchymal stem cells (MSC) during osteogenic differentiation <em>in vitro</em> showed that Has2 expression is increased while Has3 expression is decreased during differentiation. Furthermore, the complete abrogation of HA synthesis results in significantly reduced osteogenic differentiation as indicated by reduced marker gene expression (Runx-2, Tnalp, Osterix) as well as alizarin red staining. RNAseq analysis revealed that MSC from Has-tKO are characterised by decreased expression of genes annotated for bone and organ development, whereas expression of genes associated with chemokine related interactions and cytokine signalling is increased.</div><div>Taken together, we present a novel mouse model with complete deletion of HA synthases in adult mice which has the potential to study HA function in different organs and during age-related HA reduction. With respect to bone, HA synthesis is important for maintaining bone integrity, presumably based on the strong effect of HA on osteogenic differentiation.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432573","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":"Profiling of collagen and extracellular matrix deposition from cell culture using in vitro ExtraCellular matrix mass spectrometry imaging (ivECM-MSI)","authors":"Stephen C. Zambrzycki ,&nbsp;Samaneh Saberi ,&nbsp;Rachel Biggs ,&nbsp;Najmeh Eskandari ,&nbsp;Davide Delisi ,&nbsp;Harrison Taylor ,&nbsp;Anand S. Mehta ,&nbsp;Richard R. Drake ,&nbsp;Saverio Gentile ,&nbsp;Amy D. Bradshaw ,&nbsp;Michael Ostrowski ,&nbsp;Peggi M. Angel","doi":"10.1016/j.mbplus.2024.100161","DOIUrl":"10.1016/j.mbplus.2024.100161","url":null,"abstract":"<div><div>While numerous approaches have been reported towards understanding single cell regulation, there is limited understanding of single cell production of extracellular matrix phenotypes. Collagens are major proteins of the extracellular microenvironment extensively used in basic cell culture, tissue engineering, and biomedical applications. However, identifying compositional regulation of collagen remains challenging. Here, we report the development of In vitro ExtraCellular Matrix Mass Spectrometry Imaging (ivECM-MSI) as a tool to rapidly and simultaneously define collagen subtypes from coatings and basic cell culture applications. The tool uses the mass spectrometry imaging platform with reference libraries to produce visual and numerical data types. The method is highly integrated with basic in vitro strategies as it may be used with conventional cell chambers on minimal numbers of cells and with minimal changes to biological experiments. Applications tested include semi-quantitation of collagen composition in culture coatings, time course collagen deposition, deposition altered by gene knockout, and changes induced by drug treatment. This approach provides new access to proteomic information on how cell types respond to and change the extracellular microenvironment and provides a holistic understanding of both the cell and extracellular response.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427133","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":"Obesity-driven changes in breast tissue exhibit a pro-angiogenic extracellular matrix signature","authors":"Ellen E. Bamberg ,&nbsp;Mark Maslanka ,&nbsp;Kiran Vinod-Paul ,&nbsp;Sharon Sams ,&nbsp;Erica Pollack ,&nbsp;Matthew Conklin ,&nbsp;Peter Kabos ,&nbsp;Kirk C. Hansen","doi":"10.1016/j.mbplus.2024.100162","DOIUrl":"10.1016/j.mbplus.2024.100162","url":null,"abstract":"<div><div>Obesity has reached epidemic proportions in the United States, emerging as a risk factor for the onset of breast cancer and a harbinger of unfavorable outcomes <span><span>[1]</span></span>, <span><span>[2]</span></span>, <span><span>[3]</span></span>. Despite limited understanding of the precise mechanisms, both obesity and breast cancer are associated with extracellular matrix (ECM) rewiring <span><span>[4]</span></span>, <span><span>[5]</span></span>, <span><span>[6]</span></span>. Utilizing total breast tissue proteomics, we analyzed normal-weight (18.5 to &lt; 25 kg/m²), overweight (25 to &lt; 30 kg/m²), and obese (≥30 kg/m²) individuals to identify potential ECM modifying proteins for cancer development and acceleration. Obese individuals exhibited substantial ECM alterations, marked by increased basement membrane deposition, angiogenic signatures, and ECM-modifying proteins. Notably, the collagen IV crosslinking enzyme peroxidasin (PXDN) emerged as a potential mediator of the ECM changes in individuals with an elevated body mass index (BMI), strongly correlating with angiogenic and basement membrane signatures. Furthermore, glycan-binding proteins galectin-1 (LGALS1) and galectin-3 (LGALS3), which play crucial roles in matrix interactions and angiogenesis, also strongly correlate with ECM modifications. In breast cancer, elevated PXDN, LGALS1, and LGALS3 correlate with reduced relapse-free and distant-metastatic-free survival. These proteins were significantly associated with mesenchymal stromal cell markers, indicating adipocytes and fibroblasts may be the primary contributors of the obesity-related ECM changes. Our findings unveil a pro-angiogenic ECM signature in obese breast tissue, offering potential targets to inhibit breast cancer development and progression.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318518","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}