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

被引：37

作者：

Demircan, Kadir ^{[1
]}

Topcu, Vehap ^{[2
]}

Takigawa, Tomoyuki ^{[3
]}

Akyol, Sumeyya ^{[4
,5
]}

Yonezawa, Tomoko ^{[3
]}

Ozturk, Gulfer ^{[6
]}

Ugurcu, Veli ^{[7
]}

Hasgul, Rukiye ^{[4
,5
]}

Yigitoglu, M. Ramazan ^{[8
]}

Akyol, Omer ^{[9
]}

McCulloch, Daniel R. ^{[10
,11
]}

Hirohata, Satoshi ^{[3
]}

机构：

[1] Turgut Ozal Univ, Sch Med, Dept Med Biol, TR-06200 Ankara, Turkey

[2] Zekai Tahir BurakWomens Hlth Training & Res Hosp, Dept Med Genet, TR-06230 Ankara, Turkey

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Biol & Biochem, Kita Ku, Okayama 7008558, Japan

[4] Turgut Ozal Univ, Vocat Sch Hlth Sci, TR-06374 Ankara, Turkey

[5] Gaziosmanpasa Univ, Sch Med, Dept Biochem, TR-60000 Tokat, Turkey

[6] Diskapi Yildirim Beyazit Training & Res Hosp, Dept Clin Biochem, TR-06200 Ankara, Turkey

[7] Private Bilecik Orhangazi Dialysis Ctr, TR-11000 Bilecik, Turkey

[8] Turgut Ozal Univ, Sch Med, Dept Biochem, TR-06200 Ankara, Turkey

[9] Hacettepe Univ, Fac Med, Dept Biochem, TR-06200 Ankara, Turkey

[10] Deakin Univ, Fac Hlth, Sch Med, Waurn Ponds, Vic 3216, Australia

[11] Deakin Univ, Mol & Med Res SRC, Waurn Ponds, Vic 3216, Australia

来源：

BIOMED RESEARCH INTERNATIONAL | 2014年 / 2014卷

关键词：

THROMBOSPONDIN MOTIFS; EXTRACELLULAR-MATRIX; METALLOPROTEINASE; CARTILAGE; PROTEOGLYCAN; DISINTEGRIN; CLEAVAGE; DEGRADATION; DEFICIENT; FRAGMENTS;

D O I：

10.1155/2014/693746

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：8

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