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在脊髓损伤期间，ADAMTS4和ADAMTS5基因敲除小鼠可免受多功能蛋白聚糖的影响，但不能免受聚集蛋白聚糖或短蛋白聚糖的蛋白水解作用。

ADAMTS4 and ADAMTS5 knockout mice are protected from versican but not aggrecan or brevican proteolysis during spinal cord injury.

作者信息

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

机构信息

Department of Medical Biology, Turgut Ozal University School of Medicine, 06200 Ankara, Turkey.

Department of Medical Genetics, Zekai Tahir Burak Women's Health Training and Research Hospital, 06230 Ankara, Turkey.

出版信息

Biomed Res Int. 2014;2014:693746. doi: 10.1155/2014/693746. Epub 2014 Jul 3.

DOI:10.1155/2014/693746
PMID:25101296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4101972/
Abstract

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.

摘要

硫酸软骨素蛋白聚糖（CSPGs），如聚集蛋白聚糖、多功能蛋白聚糖和短蛋白聚糖，是大型聚集性细胞外基质分子，可抑制成熟中枢神经系统（CNS）的轴突生长。包括ADAMTS4和ADAMTS5在内的ADAMTS蛋白聚糖酶可降解CSPGs，这使其成为改善中枢神经系统损伤后因CSPG积累而导致的轴突生长抑制的潜在靶点。我们研究了脊髓损伤（SCI）后Adamts4或Adamts5无效等位基因纯合小鼠中CSPGs的蛋白水解情况。在Adamts4 - / -、Adamts5 - / -和野生型小鼠中观察到了ADAMTS衍生的50 - 60 kDa聚集蛋白聚糖片段和50 kDa短蛋白聚糖片段，但在假手术组中未观察到。相比之下，Adamts4 - / -和Adamts5 - / -小鼠均免受多功能蛋白聚糖蛋白水解的影响，在野生型小鼠中主要观察到ADAMTS产生的70 kDa多功能蛋白聚糖片段。通过蛋白质印迹法在SCI后的Adamts4 - / -小鼠脊髓中检测到了ADAMTS1、ADAMTS9和ADAMTS15。免疫组织化学显示损伤部位有星形胶质细胞聚集。这些数据表明，在Adamts4 - / -或Adamts5 - / -小鼠中，聚集蛋白聚糖和短蛋白聚糖的蛋白水解由ADAMTS蛋白聚糖酶家族成员代偿，但多功能蛋白聚糖蛋白水解的阈值对SCI期间单一ADAMTS蛋白聚糖酶的缺失敏感。我们展示了SCI后强大的ADAMTS活性，并举例说明了SCI期间有效清除CSPG所需的集体蛋白水解作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/698c3c2f4a99/BMRI2014-693746.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/f4e3faca455f/BMRI2014-693746.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/ecb3224cc2a1/BMRI2014-693746.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/3ac5cca6b92c/BMRI2014-693746.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/698c3c2f4a99/BMRI2014-693746.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/f4e3faca455f/BMRI2014-693746.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/ecb3224cc2a1/BMRI2014-693746.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/3ac5cca6b92c/BMRI2014-693746.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db1/4101972/698c3c2f4a99/BMRI2014-693746.004.jpg

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Biosynthesis and expression of a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats-15: a novel versican-cleaving proteoglycanase.解整合素样金属蛋白酶与血小板反应素-1 重复域 15 的生物合成与表达：一种新型的蛋白聚糖酶切割 versican。
J Biol Chem. 2013 Dec 27;288(52):37267-76. doi: 10.1074/jbc.M112.418624. Epub 2013 Nov 12.
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