View in EDS

Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis.

Saved in:
Bibliographic Details
Title: Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis.
Authors: Kabra, Harsha1 (AUTHOR), Walimbe, Tanaya1,2 (AUTHOR), Stuart, Kate1 (AUTHOR), Indey, Camille1 (AUTHOR), Jalgaonkar, Swati1 (AUTHOR), Ikwa, Elvis1 (AUTHOR), Skurnac, Taylor1 (AUTHOR), Chen, Julia1 (AUTHOR), Woolley, Andrew1 (AUTHOR), Snead, Nicholas M.1 (AUTHOR), Bachtell, Nathan1 (AUTHOR), Leeming, Diana J.3 (AUTHOR), Karsdal, Morten3 (AUTHOR), Prestwich, Glenn1,4 (AUTHOR), Panitch, Alyssa1,2 (AUTHOR) apanitch@ucdavis.edu, Paderi, John1 (AUTHOR)
Source: Biomaterials. Feb2021, Vol. 269, pN.PAG-N.PAG. 1p.
Subjects: Platelet-derived growth factor, Fibrosis, Liver cells, Blood platelet activation, Liver
Abstract: New therapeutic strategies are needed for the growing unmet clinical needs in liver disease and fibrosis. Platelet activation and PDGF activity are recognized as important therapeutic targets; however, no therapeutic approach has yet addressed these two upstream drivers of liver fibrosis. We therefore designed a matrix-targeting glycan therapeutic, SBR-294, to inhibit collagen-mediated platelet activation while also inhibiting PDGF activity. Herein we describe the synthesis and characterization of SBR-294 and demonstrate its potential therapeutic benefits in vitro and in vivo. In vitro SBR-294 was found to bind collagen (EC 50 = 23 nM), thereby inhibiting platelet-collagen engagement (IC 50 = 60 nM). Additionally, SBR-294 was found to bind all PDGF homodimeric isoforms and to inhibit PDGF-BB mediated hepatic stellate cell activation and proliferation. Translating these mechanisms in vivo , SBR-294 reduced fibrosis by up to 54% in the CCl4 mouse model (p = 0.0004), as measured by Sirius red histological analysis. Additional fibrosis measurements were also supportive of the therapeutic benefit in this model. These results support the therapeutic benefit of platelet and PDGF antagonism and warrant further investigation of SBR-294 as a potential treatment for liver fibrosis. [ABSTRACT FROM AUTHOR]
Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
FullText Text:
  Availability: 0
Header DbId: egs
DbLabel: Engineering Source
An: 148478541
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Kabra%2C+Harsha%22">Kabra, Harsha</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Walimbe%2C+Tanaya%22">Walimbe, Tanaya</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stuart%2C+Kate%22">Stuart, Kate</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Indey%2C+Camille%22">Indey, Camille</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jalgaonkar%2C+Swati%22">Jalgaonkar, Swati</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ikwa%2C+Elvis%22">Ikwa, Elvis</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Skurnac%2C+Taylor%22">Skurnac, Taylor</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Julia%22">Chen, Julia</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Woolley%2C+Andrew%22">Woolley, Andrew</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Snead%2C+Nicholas+M%2E%22">Snead, Nicholas M.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bachtell%2C+Nathan%22">Bachtell, Nathan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Leeming%2C+Diana+J%2E%22">Leeming, Diana J.</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Karsdal%2C+Morten%22">Karsdal, Morten</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Prestwich%2C+Glenn%22">Prestwich, Glenn</searchLink><relatesTo>1,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Panitch%2C+Alyssa%22">Panitch, Alyssa</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> apanitch@ucdavis.edu</i><br /><searchLink fieldCode="AR" term="%22Paderi%2C+John%22">Paderi, John</searchLink><relatesTo>1</relatesTo> (AUTHOR)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Feb2021, Vol. 269, pN.PAG-N.PAG. 1p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Platelet-derived+growth+factor%22">Platelet-derived growth factor</searchLink><br /><searchLink fieldCode="DE" term="%22Fibrosis%22">Fibrosis</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+cells%22">Liver cells</searchLink><br /><searchLink fieldCode="DE" term="%22Blood+platelet+activation%22">Blood platelet activation</searchLink><br /><searchLink fieldCode="DE" term="%22Liver%22">Liver</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: New therapeutic strategies are needed for the growing unmet clinical needs in liver disease and fibrosis. Platelet activation and PDGF activity are recognized as important therapeutic targets; however, no therapeutic approach has yet addressed these two upstream drivers of liver fibrosis. We therefore designed a matrix-targeting glycan therapeutic, SBR-294, to inhibit collagen-mediated platelet activation while also inhibiting PDGF activity. Herein we describe the synthesis and characterization of SBR-294 and demonstrate its potential therapeutic benefits in vitro and in vivo. In vitro SBR-294 was found to bind collagen (EC 50 = 23 nM), thereby inhibiting platelet-collagen engagement (IC 50 = 60 nM). Additionally, SBR-294 was found to bind all PDGF homodimeric isoforms and to inhibit PDGF-BB mediated hepatic stellate cell activation and proliferation. Translating these mechanisms in vivo , SBR-294 reduced fibrosis by up to 54% in the CCl4 mouse model (p = 0.0004), as measured by Sirius red histological analysis. Additional fibrosis measurements were also supportive of the therapeutic benefit in this model. These results support the therapeutic benefit of platelet and PDGF antagonism and warrant further investigation of SBR-294 as a potential treatment for liver fibrosis. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=148478541
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.biomaterials.2020.120538
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 1
        StartPage: N.PAG
    Subjects:
      – SubjectFull: Platelet-derived growth factor
        Type: general
      – SubjectFull: Fibrosis
        Type: general
      – SubjectFull: Liver cells
        Type: general
      – SubjectFull: Blood platelet activation
        Type: general
      – SubjectFull: Liver
        Type: general
    Titles:
      – TitleFull: Localized inhibition of platelets and platelet derived growth factor by a matrix targeted glycan mimetic significantly attenuates liver fibrosis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Kabra, Harsha
      – PersonEntity:
          Name:
            NameFull: Walimbe, Tanaya
      – PersonEntity:
          Name:
            NameFull: Stuart, Kate
      – PersonEntity:
          Name:
            NameFull: Indey, Camille
      – PersonEntity:
          Name:
            NameFull: Jalgaonkar, Swati
      – PersonEntity:
          Name:
            NameFull: Ikwa, Elvis
      – PersonEntity:
          Name:
            NameFull: Skurnac, Taylor
      – PersonEntity:
          Name:
            NameFull: Chen, Julia
      – PersonEntity:
          Name:
            NameFull: Woolley, Andrew
      – PersonEntity:
          Name:
            NameFull: Snead, Nicholas M.
      – PersonEntity:
          Name:
            NameFull: Bachtell, Nathan
      – PersonEntity:
          Name:
            NameFull: Leeming, Diana J.
      – PersonEntity:
          Name:
            NameFull: Karsdal, Morten
      – PersonEntity:
          Name:
            NameFull: Prestwich, Glenn
      – PersonEntity:
          Name:
            NameFull: Panitch, Alyssa
      – PersonEntity:
          Name:
            NameFull: Paderi, John
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 02
              Text: Feb2021
              Type: published
              Y: 2021
          Identifiers:
            – Type: issn-print
              Value: 01429612
          Numbering:
            – Type: volume
              Value: 269
          Titles:
            – TitleFull: Biomaterials
              Type: main
ResultId 1