Cargando…

ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential tar...

Descripción completa

Detalles Bibliográficos
Autores principales: Demircan, Kadir, Topcu, Vehap, Takigawa, Tomoyuki, Akyol, Sumeyya, Yonezawa, Tomoko, Ozturk, Gulfer, Ugurcu, Veli, Hasgul, Rukiye, Yigitoglu, M. Ramazan, Akyol, Omer, McCulloch, Daniel R., Hirohata, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101972/
https://www.ncbi.nlm.nih.gov/pubmed/25101296
http://dx.doi.org/10.1155/2014/693746
_version_ 1782480987370815488
author Demircan, Kadir
Topcu, Vehap
Takigawa, Tomoyuki
Akyol, Sumeyya
Yonezawa, Tomoko
Ozturk, Gulfer
Ugurcu, Veli
Hasgul, Rukiye
Yigitoglu, M. Ramazan
Akyol, Omer
McCulloch, Daniel R.
Hirohata, Satoshi
author_facet Demircan, Kadir
Topcu, Vehap
Takigawa, Tomoyuki
Akyol, Sumeyya
Yonezawa, Tomoko
Ozturk, Gulfer
Ugurcu, Veli
Hasgul, Rukiye
Yigitoglu, M. Ramazan
Akyol, Omer
McCulloch, Daniel R.
Hirohata, Satoshi
author_sort Demircan, Kadir
collection PubMed
description The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4−/−, Adamts5−/−, and wt mice but not in the sham-operated group. By contrast Adamts4−/− and Adamts5−/− mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4−/− mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4−/− or Adamts5−/− mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI.
format Online
Article
Text
id pubmed-4101972
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-41019722014-08-06 ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury Demircan, Kadir Topcu, Vehap Takigawa, Tomoyuki Akyol, Sumeyya Yonezawa, Tomoko Ozturk, Gulfer Ugurcu, Veli Hasgul, Rukiye Yigitoglu, M. Ramazan Akyol, Omer McCulloch, Daniel R. Hirohata, Satoshi Biomed Res Int Research Article The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50–60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4−/−, Adamts5−/−, and wt mice but not in the sham-operated group. By contrast Adamts4−/− and Adamts5−/− mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4−/− mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4−/− or Adamts5−/− mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI. Hindawi Publishing Corporation 2014 2014-07-03 /pmc/articles/PMC4101972/ /pubmed/25101296 http://dx.doi.org/10.1155/2014/693746 Text en Copyright © 2014 Kadir Demircan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Demircan, Kadir
Topcu, Vehap
Takigawa, Tomoyuki
Akyol, Sumeyya
Yonezawa, Tomoko
Ozturk, Gulfer
Ugurcu, Veli
Hasgul, Rukiye
Yigitoglu, M. Ramazan
Akyol, Omer
McCulloch, Daniel R.
Hirohata, Satoshi
ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title_full ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title_fullStr ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title_full_unstemmed ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title_short ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury
title_sort adamts4 and adamts5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101972/
https://www.ncbi.nlm.nih.gov/pubmed/25101296
http://dx.doi.org/10.1155/2014/693746
work_keys_str_mv AT demircankadir adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT topcuvehap adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT takigawatomoyuki adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT akyolsumeyya adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT yonezawatomoko adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT ozturkgulfer adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT ugurcuveli adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT hasgulrukiye adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT yigitoglumramazan adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT akyolomer adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT mccullochdanielr adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury
AT hirohatasatoshi adamts4andadamts5knockoutmiceareprotectedfromversicanbutnotaggrecanorbrevicanproteolysisduringspinalcordinjury