Proteoglycan research最新文献

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":null,"pages":null},"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":null,"pages":null},"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

VAR2HP recognizing heparin‐like epitopes in targeted therapy and diagnosis of tumors 在肿瘤靶向治疗和诊断中识别肝素样表位的 VAR2HP

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.16

Yingying Xu, Yi Liu, Ruyi Zou, Xunyi Yuan, Lin Wei, Yong Qin, Xu Wang, Yunxue Zhao, Zhenqiu Yang, Wenshuang Wang, Fuchuan Li

{"title":"VAR2HP recognizing heparin‐like epitopes in targeted therapy and diagnosis of tumors","authors":"Yingying Xu, Yi Liu, Ruyi Zou, Xunyi Yuan, Lin Wei, Yong Qin, Xu Wang, Yunxue Zhao, Zhenqiu Yang, Wenshuang Wang, Fuchuan Li","doi":"10.1002/pgr2.16","DOIUrl":"https://doi.org/10.1002/pgr2.16","url":null,"abstract":"The synthesis of glycosaminoglycans (GAGs) in vivo occurs with high spatiotemporal specificity, and any aberrant expression of GAGs is closely related to the occurrence of diseases. In terms of tumorigenesis, the abnormally expressed GAGs have become a potential target for the diagnosis and therapy of tumors. As previously reported, VAR2HP, a protein probe that recognizes the unique heparin (Hep)‐like epitopes, interacts with a decasaccharide structure containing at least three HexA2S(1‐4)GlcNS6S disaccharides. Its recognition epitopes are overexpressed in various tumor cells and appear promising as target molecules of multiple tumors. Herein, we found that VAR2HP used as an antineoplastic carrier could promote drug enrichment in tumor sites by targeting the specific Hep‐like epitopes on tumor cells, thereby reducing the damage to normal cells in vitro and in vivo. Moreover, VAR2HP acting on cells alone could inhibit cell proliferation, indicating that VAR2HP as a drug carrier has a dual effect of antitumor activity. Additionally, we observed that VAR2HP significantly stained cancer tissues more strongly than neighboring nonmalignant tissues. The staining was competitively inhibited by added exogenous Hep, indicating that the Hep‐like epitopes recognized by VAR2HP were a potential target molecule in tumor diagnosis. Moreover, the VAR2HP‐bound Hep‐like epitopes were found to be overexpressed in the sera of patients with hepatocellular carcinoma (HCC) but not in normal persons and patients with cirrhosis. Taken together, this study shows that VAR2HP and its heparin‐like epitopes have great potential in targeted therapy of tumors and HCC diagnosis.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140520843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting glypicans through EGFR and JAK/STAT signaling axes drives breast cancer progression 通过表皮生长因子受体和 JAK/STAT 信号轴靶向糖蛋白，推动乳腺癌进展

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.18

Paraskevi Ioannou, Kyriaki Tzaferi, Christos Koutsakis, Z. Piperigkou, Nikos K. Karamanos

{"title":"Targeting glypicans through EGFR and JAK/STAT signaling axes drives breast cancer progression","authors":"Paraskevi Ioannou, Kyriaki Tzaferi, Christos Koutsakis, Z. Piperigkou, Nikos K. Karamanos","doi":"10.1002/pgr2.18","DOIUrl":"https://doi.org/10.1002/pgr2.18","url":null,"abstract":"Extracellular matrix (ECM) and its dynamic remodeling contribute to the progression of breast cancer, the most prevailing cancer type in women. Glypicans (GPCs) function as cell co‐receptors by facilitating the formation of ligand–receptor complexes. An important regulator in the context of breast cancer progression is the JAK/STAT signaling pathway that oversees the expression of genes associated with cancer cell characteristics. Epidermal growth factor receptor (EGFR) is a pivotal player in this process. The aim of this study is to examine the effect of the EGFR and JAK/STAT signaling pathways on GPCs expression in breast cancer cells with different estrogen receptor (ER) status, depicting different breast cancer subtypes. To this end, the ERα‐positive MCF‐7, and the ERβ‐positive MDA‐MB‐231 breast cancer cell lines were evaluated in terms of the impact of downstream inhibition of both pathways on the functional properties as well as the expression of GPCs 1‐6 genes. Notably, the downstream inhibition of both EGFR and JAK/STAT cascades mitigate cell proliferation and migration, while increasing cell adhesion on collagen type I in an ER‐independent manner. However, the inhibition exhibited a cell‐line‐dependent effect on GPC expression, as in MCF‐7 cells GPCs expression is mostly downregulated excepting GPC‐4 and GPC‐5. Conversely, in MDA‐MB‐231 cells, EGFR and JAK/STAT activation is essential for maintaining GPCs at low levels. Additionally, STRING analysis identified the small leucine‐rich PG decorin as a putative link between all GPCs and EGFR. Subsequently, a deeper understanding on the effect of EGFR and JAK/STAT signaling may shed light into the role and interplay between GPCs and decorin in breast cancer progression, thus contributing to novel therapeutic solutions.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140524082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia Covid-19和非Covid-19肺炎中的肝素酶-1和MMPs

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.14

V. Masola, G. Marrone, Carola Condoluci, Marco Franchi, Leonardo Stella, M. Biolato, Luca Miele, Giovanni Gambaro, Claudia Dal Vecchio, M. Onisto

{"title":"Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia","authors":"V. Masola, G. Marrone, Carola Condoluci, Marco Franchi, Leonardo Stella, M. Biolato, Luca Miele, Giovanni Gambaro, Claudia Dal Vecchio, M. Onisto","doi":"10.1002/pgr2.14","DOIUrl":"https://doi.org/10.1002/pgr2.14","url":null,"abstract":"Together with the ACE2 protein, heparan sulfate present at the level of the glycocalyx in the lung epithelia is considered a cellular “co‐receptor” for the viral spike protein that allows severe acute respiratory syndrome coronavirus 2 (SARS‐CoV) to infect cells. An increase in the amount and activity of heparanase‐1 (HPSE), the only enzyme capable of degrading the heparan sulfate (HS) chains of the glycocalyx and of the extracellular matrix, has been described in the plasma of patients affected by coronavirus disease 2019 (Covid‐19). Furthermore, the activity of matrix metalloproteases, or MMPs, has been related to matrix degradation, oxidative stress, and inflammation in Covid‐19 patients. In this study, we enrolled 26 Covid‐19 patients and 15 controls with diagnosis of non‐SARS‐CoV‐2‐related pneumonia. We evaluated the expression and activity of HPSE and the expression of MMPs in their serum together with other clinical markers of disease and inflammation. Results proved that HPSE expression and activity serum levels were significantly increased, whereas MMP2 and 9 were decreased in Covid‐19 versus non‐Covid‐19 pneumonia patients. In addition, IL‐6 levels were higher, whereas platelet and white blood cells were lower in Covid‐19 with respect to non‐Covid‐19 pneumonia. Moreover, MMP9 but not HPSE (expression and activity) levels were increased in Covid‐19 pneumonia patients with ongoing lung alteration over time. In summary, the present findings indicate that HPSE and MMPs are differentially regulated in Covid‐19 and non‐Covid‐19 pneumonia.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140523712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo activities of heparan sulfate differentially modified by NDSTs during development 发育过程中被 NDSTs 不同修饰的硫酸肝素的体内活性

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.17

E. Nakato, Sarah Baker, A. Kinoshita-Toyoda, Collin Knudsen, Yi‐Si Lu, Masahiko Takemura, Hidenao Toyoda, H. Nakato

{"title":"In vivo activities of heparan sulfate differentially modified by NDSTs during development","authors":"E. Nakato, Sarah Baker, A. Kinoshita-Toyoda, Collin Knudsen, Yi‐Si Lu, Masahiko Takemura, Hidenao Toyoda, H. Nakato","doi":"10.1002/pgr2.17","DOIUrl":"https://doi.org/10.1002/pgr2.17","url":null,"abstract":"Heparan sulfate proteoglycans (HSPGs) serve as co‐receptors for growth factor signaling during development. It is well known that the level and patterns of sulfate groups of heparan sulfate (HS) chains, or HS fine structures, have a major impact on HSPG function. On the other hand, the physiological significance of other structural features of HS, including NS/NA domain organization, remains to be elucidated. A blueprint of the HS domain structures is mainly controlled by HS N‐deacetylase/N‐sulfotransferases (NDSTs). To analyze in vivo activities of differentially modified HS, we established two knock‐in (KI) Drosophila strains with the insertion of mouse Ndst1 (mNdst1) or Ndst2 (mNdst2) in the locus of sulfateless (sfl), the only Drosophila NDST. In these KI lines, mNDSTs are expressed from the sfl locus, in the level and patterns identical to the endogenous sfl gene. Thus, phenotypes of Ndst1 KI and Ndst2KI animals reflect the ability of HS structures made by these enzymes to rescue sfl mutation. Remarkably, we found that mNdst1 completely rescued the loss of sfl. mNdst2 showed a limited rescue ability, despite a higher level of HS sulfation compared to HS in mNdst1 KI. Our study suggests that independent of sulfation levels, additional HS structural features controlled by NDSTs play key roles during tissue patterning.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140524922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel biomimetic probe for galectin‐3 recognition: Chemical synthesis and structural characterization of a β‐galactose branched sodium hyaluronate 识别 galectin-3 的新型仿生物探针：β-半乳糖支链透明质酸钠的化学合成与结构表征

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.19

Sofia Nizzolo, Emiliano Esposito, Ming‐Hong Ni, Laura Bertocchi, Giulio Bianchini, Nadia Freato, Serena Zanzoni, Marco Guerrini, Sabrina Bertini

{"title":"A novel biomimetic probe for galectin‐3 recognition: Chemical synthesis and structural characterization of a β‐galactose branched sodium hyaluronate","authors":"Sofia Nizzolo, Emiliano Esposito, Ming‐Hong Ni, Laura Bertocchi, Giulio Bianchini, Nadia Freato, Serena Zanzoni, Marco Guerrini, Sabrina Bertini","doi":"10.1002/pgr2.19","DOIUrl":"https://doi.org/10.1002/pgr2.19","url":null,"abstract":"Sodium hyaluronate (HA), a derivative of hyaluronan, is a natural and biocompatible polysaccharide that interacts with cluster of differentiation‐44 receptor to promote fine‐tuning of inflammation, fibrosis, and tissue remodeling. HA has a smaller molecular weight than hyaluronan and is overall more stable being less prone to oxidation. In this study, we report a novel lactose‐functionalized sodium hyaluronate, named HYLACH®. Functionalization with multiple β‐galactose residues facilitates its interaction with galectin‐3, a β‐galactose binding lectin implicated in various pathological processes including inflammation, host defense, and fibrosis, especially critical in idiopathic pulmonary fibrosis (IPF). Our strategy was to modify HA, to varying extents, at carboxyl sites with 1‐amino‐1‐deoxy‐lactitol, in the presence of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methyl morpholinium chloride in aqueous media. We characterized the chemical structure, molecular weight, and degree of substitution of HYLACH® using NMR spectroscopy and size exclusion chromatography. We further determined several key parameters including its stability toward enzymatic degradation and the binding affinity and conformational changes of galectin‐3 interaction with HYLACH®. Collectively, the generation of a novel functionalized HA with an ability to bind and suppress galectin‐3 function, in combination with safety and biocompatibility, offers the opportunity to test this compound in therapeutic trials of devastating fibrotic diseases such as IPF.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140515769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chondroitin sulfate proteoglycan promotes APRIL‐induced tumor cell proliferation 硫酸软骨素蛋白多糖促进 APRIL 诱导的肿瘤细胞增殖

Proteoglycan research Pub Date : 2024-01-01 DOI: 10.1002/pgr2.15

S. Nadanaka, Toshiyasu Koike, Hiroshi Kitagawa

{"title":"Chondroitin sulfate proteoglycan promotes APRIL‐induced tumor cell proliferation","authors":"S. Nadanaka, Toshiyasu Koike, Hiroshi Kitagawa","doi":"10.1002/pgr2.15","DOIUrl":"https://doi.org/10.1002/pgr2.15","url":null,"abstract":"A proliferation‐inducing ligand (APRIL), a member of the tumor necrosis factor superfamily, affects the survival and proliferation of tumor cells. Understanding the mechanism of action of APRIL in tumor cells, including intracellular signaling, is important for its potential use in diagnostics and prognosis. It has been shown that APRIL‐induced tumor proliferation requires heparan sulfate (HS) proteoglycans to mediate the binding of APRIL to tumor cells. Here, we show that chondroitin sulfate (CS) proteoglycan mainly contributes to the APRIL‐stimulated proliferation of triple‐negative breast cancer BT‐549 cells. Knockout of chondroitin 4‐O‐sulfotransferase‐1 (C4ST‐1), a key CS biosynthetic enzyme, suppressed APRIL‐induced tumor proliferation, whereas deficiency of exostosin 1 (EXT1), a key HS biosynthetic enzyme, had only weak effects. Molecular interaction analyses using Biacore revealed that although CS did not directly bind to tumor growth through Ca2+ modulator interactor (TACI), it enhanced the binding of APRIL to the APRIL receptor, TACI. The small leucine‐rich proteoglycan, biglycan, plays a pivotal role in tumor growth and progression. Biglycan knockdown inhibited BT‐549 cell proliferation. These results suggest that CS synthesized by C4ST‐1 participates in APRIL signaling and modulates pathological events in tumors.","PeriodicalId":74585,"journal":{"name":"Proteoglycan research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139633520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Versican and versikine: The dynamism of the extracellular matrix Versican和versikine：细胞外基质的活力

Proteoglycan research Pub Date : 2023-10-01 DOI: 10.1002/pgr2.13

Hideto Watanabe

引用次数: 0

The functional network of biglycan: A new frontier in tumor progression biglycan的功能网络:肿瘤进展的新前沿

Proteoglycan research Pub Date : 2023-07-01 DOI: 10.1002/pgr2.11

Li Yu, Nako Maishi, Aya Matsuda, Kyoko Hida

引用次数: 1