Proteoglycan research最新文献

Chemoenzymatic synthesis with the Pasteurella hyaluronan synthase; production of a multitude of defined authentic, derivatized, and analog polymers. 巴氏杆菌透明质酸合成酶的化学酶合成生产大量的定义真实的，衍生的，和模拟聚合物。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-10-06 DOI: 10.1002/pgr2.70000

Paul L DeAngelis

{"title":"Chemoenzymatic synthesis with the Pasteurella hyaluronan synthase; production of a multitude of defined authentic, derivatized, and analog polymers.","authors":"Paul L DeAngelis","doi":"10.1002/pgr2.70000","DOIUrl":"10.1002/pgr2.70000","url":null,"abstract":"Hyaluronan (HA; [-3-GlcNAc-1-beta-4-GlcA-1-beta] n ), an essential matrix polysaccharide of vertebrates and the molecular camouflage coating in certain pathogens, is polymerized by \"HA synthase\" (HAS) enzymes. Three HAS classes have been identified with biotechnological utility, but only the Class II PmHAS from Pasteurella multocida Type A has been useful for preparation of very defined HA polymers in vitro. Two general chemoenzymatic strategies with different size products are possible: (1) repetitive step-wise extension reactions by sequential addition of a single monosaccharide from a donor UDP-sugar onto an acceptor (or \"primer\") comprised of a short glycosaminoglycan chain (e.g., HA di-, tri- or tetrasaccharide) or an artificial glucuronide yielding homogeneous oligosaccharides in the range of 2 to ~20 monosaccharide units (n = 1 to ~10), or (2) \"one-pot\" polymerization reactions employing acceptor-mediated synchronization with stoichiometric size control yielding quasi-monodisperse (i.e., polydispersity approaching 1; very narrow size distributions) polysaccharides in the range of ~7 kDa to ~2 MDa (n = ~17 to 5000). In either strategy, acceptors containing non-carbohydrate functionalities (e.g., biotin, fluorophores, amines) can add useful moieties to the reducing termini of HA chains at 100% efficiency. As a further structural diversification, PmHAS can utilize a variety of unnatural UDP-sugar analogs thus adding novel groups (e.g., trifluoroacetyl, alkyne, azide, sulfhydryl) along the HA backbone and/or at its nonreducing terminus. This review discusses the current understanding and recent advances in HA chemoenzymatic synthesis methods using PmHAS. This powerful toolbox has potential for creation of a multitude of HA-based probes, therapeutics, drug conjugates, coatings, and biomaterials.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11673988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904164","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}

引用次数: 0

A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer. glypican-3相互作用伙伴的蛋白质组学图谱：甲胎蛋白和其他细胞外蛋白作为肝癌潜在免疫治疗靶点的鉴定

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-10-06 DOI: 10.1002/pgr2.70004

Yi-Fan Zhang, Shaoli Lin, Xiao Zhen, Mitchell Ho

{"title":"A proteomic atlas of glypican-3 interacting partners: Identification of alpha-fetoprotein and other extracellular proteins as potential immunotherapy targets in liver cancer.","authors":"Yi-Fan Zhang, Shaoli Lin, Xiao Zhen, Mitchell Ho","doi":"10.1002/pgr2.70004","DOIUrl":"10.1002/pgr2.70004","url":null,"abstract":"Antibody and cell-based therapeutics targeting cell surface receptors have emerged as a major class of immune therapeutics for treating cancer. However, the number of cell surface targets for cancer immunotherapy remains limited. Glypican-3 (GPC3) is a cell surface proteoglycan and an oncofetal antigen. In this study, we report a large-scale tumor-associated GPC3 co-immunoprecipitation (CoIP)-proteomic study using liver cancer xenograft tumors in mice. We identified 153 GPC3-associated proteins through mass spectrometry. To identify potential drug targets, we categorized GPC3-associated proteins based on their subcellular locations using UniProt annotations, with a focus on extracellular proteins. Additionally, we annotated differentially expressed proteins in hepatocellular carcinoma (HCC) versus non-tumor liver samples based on the literature, analyzed expression levels in tumor versus normal tissues using TCGA and GTEx databases via GEPIA, and identified prognostic liver cancer markers according to GEPIA. Among GPC3-associated proteins, Immunoglobulin Superfamily Member 1 (IGSF1), alpha-fetoprotein (AFP), FAT Atypical Cadherin 1 (FAT1), Formin 1 (FMN1), and Guanylate Cyclase 2C (GUCY2C), were identified as potential therapeutic targets. Furthermore, we validated the direct protein interaction between GPC3 and AFP through immunoprecipitation with purified proteins and through co-localization imaging using immunofluorescence microscopy. This study provides large proteomic datasets related to GPC3-associated proteins, enhancing our understanding of glypican biology in cancer cells and offering a new approach to identifying immunotherapy targets.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018015","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}

引用次数: 0

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling. 作为病理细胞外基质重塑生物标志物的可溶性蛋白聚糖和蛋白聚糖片段。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-16 DOI: 10.1002/pgr2.70011

Marsioleda Kemberi, Alexander F Minns, Salvatore Santamaria

引用次数: 0

High-fidelity and iterative affinity extraction of hyaluronan. 透明质酸的高保真迭代亲和提取。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-12-06 DOI: 10.1002/pgr2.70008

Dorothea A Erxleben, Felipe Rivas, Ian Smith, Suruchi Poddar, Paul L DeAngelis, Elaheh Rahbar, Adam R Hall

引用次数: 0

Injury From Nematode Lung Migration Induces an IL-13-Dependent Hyaluronan Matrix. 线虫肺迁移造成的损伤诱导了一种依赖于 IL-13 的透明质酸基质

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-25 DOI: 10.1002/pgr2.70012

Rebecca J Dodd, Dora Moffatt, Monika Vachiteva, James E Parkinson, Brian H K Chan, Anthony J Day, Judith E Allen, Tara E Sutherland

{"title":"Injury From Nematode Lung Migration Induces an IL-13-Dependent Hyaluronan Matrix.","authors":"Rebecca J Dodd, Dora Moffatt, Monika Vachiteva, James E Parkinson, Brian H K Chan, Anthony J Day, Judith E Allen, Tara E Sutherland","doi":"10.1002/pgr2.70012","DOIUrl":"10.1002/pgr2.70012","url":null,"abstract":"A consistent feature of lung injury is a rapid and sustained accumulation of hyaluronan (HA). The rodent gut-dwelling nematode Nippostrongylus brasiliensis (Nb) induces tissue damage as it migrates through the lungs. Type 2 immune responses are essential for the repair of the lungs, hence Nb infection is a well-established model to study immune-mediated lung repair. We found that Nb infection was associated with increased HA in the lung, which peaked at d7 post-infection (p.i.). Deposition of HA in the alveolar epithelium correlated with regions of damaged tissue and the type 2 immune response, which is characterized by eosinophilia and increased type 2 cytokines such as IL-13. Consistent with the accumulation of HA, we observed increased expression of the major synthase Has2, alongside decreased expression of Hyal1, Hyal2, and Tmem2, which can degrade existing HA. Expression of Tsg6 was also increased and correlated with the presence of inter-α-inhibitor heavy chain-HA complexes (HC·HA) at d7 p.i. Using IL-13-deficient mice, we found that the accumulation of HA during Nb infection was IL-13 dependent. Our data thus provide further evidence that IL-13 is a modulator of the HA matrix during lung challenge and links IL-13-mediated HA regulation to tissue repair pathways.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":"e70012"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741472","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}

引用次数: 0

Utility of Authentic ¹³C-Labeled Disaccharide to Calibrate Hyaluronan Content Measurements by LC-MS. 利用 13C 标记的真品二糖校准 LC-MS 测量的透明质酸含量。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-05 DOI: 10.1002/pgr2.70010

Eduardo Stancanelli, Dixy E Green, Katelyn Arnold, Jianxiang Zhang, Deyu Kong, Paul L DeAngelis, Jian Liu

{"title":"Utility of Authentic 13C-Labeled Disaccharide to Calibrate Hyaluronan Content Measurements by LC-MS.","authors":"Eduardo Stancanelli, Dixy E Green, Katelyn Arnold, Jianxiang Zhang, Deyu Kong, Paul L DeAngelis, Jian Liu","doi":"10.1002/pgr2.70010","DOIUrl":"10.1002/pgr2.70010","url":null,"abstract":"Hyaluronan (hyaluronic acid, HA), a key glycosaminoglycan in the extracellular matrix, plays crucial roles in various physiological and pathological processes, including development, tissue hydration, inflammation, and tumor progression. Traditional methods for HA quantification, such as ELISA-like assays, often have limitations in sensitivity and specificity, particularly for lower molecular weight HA. In this work, we introduce a coupled liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method that employs a chemoenzymatically synthesized 13C-labeled lyase-derived authentic HA disaccharide calibrant for quantification of HA at the nanogram level. The method was validated against three HA polysaccharides with the sizes of ~33, 210, and 540 kDa. We applied this quantification technique to mouse tissues and plasma from both healthy and acetaminophen-induced acute liver injury mice. Our data revealed a ~75-fold increase in HA concentration in the liver of acetaminophen-injured mice with a concomitant depletion from plasma. Overall, our method offers a robust, universal, and highly sensitive tool for HA analysis in diverse biological samples that will advance the investigation of the roles of this polysaccharide in human disease conditions.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 4","pages":"e70010"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712126","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}

引用次数: 0

Chondroitin sulfate in invertebrate development. 无脊椎动物发育中的硫酸软骨素。

Proteoglycan research Pub Date : 2024-10-01 Epub Date: 2024-11-05 DOI: 10.1002/pgr2.70009

Ayano Moriya, Eriko Nakato, Jin-Ping Li, Hiroshi Nakato

引用次数: 0

The spatial separation of basic amino acids is similar in RHAMM and hyaluronan binding peptide P15-1 despite different sequences and conformations. 尽管 RHAMM 和透明质酸结合肽 P15-1 的序列和构象不同，但其碱性氨基酸的空间分隔相似。

Proteoglycan research Pub Date : 2024-07-01 Epub Date: 2024-09-10 DOI: 10.1002/pgr2.70001

Mehmet Emre Erkanli, Ted Keunsil Kang, Thorsten Kirsch, Eva A Turley, Jin Ryoun Kim, Mary K Cowman

{"title":"The spatial separation of basic amino acids is similar in RHAMM and hyaluronan binding peptide P15-1 despite different sequences and conformations.","authors":"Mehmet Emre Erkanli, Ted Keunsil Kang, Thorsten Kirsch, Eva A Turley, Jin Ryoun Kim, Mary K Cowman","doi":"10.1002/pgr2.70001","DOIUrl":"https://doi.org/10.1002/pgr2.70001","url":null,"abstract":"Peptides that increase pro-reparative responses to injury and disease by modulating the functional organization of hyaluronan (HA) with its cell surface binding proteins (e.g., soluble receptor for hyaluronan-mediated motility [RHAMM] and integral membrane CD44) have potential therapeutic value. The binding of RHAMM to HA is an attractive target, since RHAMM is normally absent or expressed at low levels in homeostatic conditions, but its expression is significantly elevated in the extracellular matrix during tissue stress, response-to-injury, and in cancers and inflammation-based diseases. The HA-binding site in RHAMM contains two closely spaced sequences of clustered basic amino acids, in an alpha-helical conformation. In the present communication, we test whether an alpha-helical conformation is required for effective peptide binding to HA, and competitive disruption of HA-RHAMM interaction. The HA-binding RHAMM-competitive peptide P15-1, identified using the unbiased approach of phage display, was examined using circular dichroism spectroscopy and the conformation-predictive AI-based AlphaFold2 algorithm. Unlike the HA-binding site in RHAMM, peptide P15-1 was found to adopt irregular conformations in solution rather than alpha helices. Instead, our structural analysis suggests that the primary determinant of peptide-HA binding is associated with a specific clustering and spacing pattern of basic amino acids, allowing favorable electrostatic interaction with carboxylate groups on HA.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 3","pages":"e70001"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302908","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}

引用次数: 0

Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy. 基底膜的蛋白多糖：血管生成、神经发生和自噬的关键控制者

Proteoglycan research Pub Date : 2024-07-01 Epub Date: 2024-06-29 DOI: 10.1002/pgr2.22

Maurizio Mongiat, Gabriel Pascal, Evelina Poletto, Davion M Williams, Renato V Iozzo

{"title":"Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy.","authors":"Maurizio Mongiat, Gabriel Pascal, Evelina Poletto, Davion M Williams, Renato V Iozzo","doi":"10.1002/pgr2.22","DOIUrl":"10.1002/pgr2.22","url":null,"abstract":"Anti-angiogenic therapy is an established method for the treatment of several cancers and vascular-related diseases. Most of the agents employed target the vascular endothelial growth factor A, the major cytokine stimulating angiogenesis. However, the efficacy of these treatments is limited by the onset of drug resistance. Therefore, it is of fundamental importance to better understand the mechanisms that regulate angiogenesis and the microenvironmental cues that play significant role and influence patient treatment and outcome. In this context, here we review the importance of the three basement membrane heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin and collagen XVIII. These HSPGs are abundantly expressed in the vasculature and, due to their complex molecular architecture, they interact with multiple endothelial cell receptors, deeply affecting their function. Under normal conditions, these proteoglycans exert pro-angiogenic functions. However, in pathological conditions such as cancer and inflammation, extracellular matrix remodeling leads to the degradation of these large precursor molecules and the liberation of bioactive processed fragments displaying potent angiostatic activity. These unexpected functions have been demonstrated for the C-terminal fragments of perlecan and collagen XVIII, endorepellin and endostatin. These bioactive fragments can also induce autophagy in vascular endothelial cells which contributes to angiostasis. Overall, basement membrane proteoglycans deeply affect angiogenesis counterbalancing pro-angiogenic signals during tumor progression, and represent possible means to develop new prognostic biomarkers and novel therapeutic approaches for the treatment of solid tumors.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057454","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}

引用次数: 0

Clearing the light path: proteoglycans and their important roles in the lens and cornea. 清除光路：蛋白聚糖及其在晶状体和角膜中的重要作用。

Proteoglycan research Pub Date : 2024-04-01 Epub Date: 2024-05-08 DOI: 10.1002/pgr2.20

Mary Ann Stepp, A Sue Menko

{"title":"Clearing the light path: proteoglycans and their important roles in the lens and cornea.","authors":"Mary Ann Stepp, A Sue Menko","doi":"10.1002/pgr2.20","DOIUrl":"10.1002/pgr2.20","url":null,"abstract":"Some of the earliest studies of glycans were performed on mammalian corneas and lenses with many of the key concepts we currently recognize as being fundamental to our understanding of basic cell biology arising from these studies. Proteoglycans and their GAG side chains are essential components of the ECM of the lens capsule. They also are present in the anterior corneal epithelial basement membrane and the posterior (Decemet's) basement membrane, and they organize collagen fiber diameters and spacing in the corneal stroma to maintain stromal clarity. Studies using genetically engineered mice and characterization of spontaneously arising mutations in genes controlling proteoglycan synthesis have generated new insight into the roles played by proteoglycans in signal transduction. We now know that proteoglycans and GAGs can regulate cell signaling and the maintenance of avascularity and immune privilege that are hallmarks of these tissues. In addition, proteoglycan-rich matrices provide the pathways for immune cells to populate the surface of the lens as a response to corneal wounding and in a model of Experimental Autoimmune Uveitis. Here we describe what is known about proteoglycans and GAGs in the cornea and lens. This knowledge has begun to provide promising leads into new proteoglycan-based treatments aimed at restoring and maintaining homeostasis in the cornea. Future studies are needed to determine how these new drugs impact the recruitment of immune cells to the lens for functions in restoring/maintaining homeostasis in the eye.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683784","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}

引用次数: 0