Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury.
Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury.
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DOI：
10.1186/s12974-018-1123-7
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发表时间：
2018-03-20
影响因子：
9.3
通讯作者：
Shubayev VI
中科院分区：
文献类型：
--
作者：
Remacle AG;Hullugundi SK;Dolkas J;Angert M;Chernov AV;Strongin AY;Shubayev VI
在周围神经中，促炎基质金属蛋白酶 (MMP)-9 在对损伤的急性反应中发挥重要作用。 MMP-9 活性是否会导致晚期损伤，或者神经损伤后 MMP-9 的表达或活性是否具有性二态性仍然未知。在雌性和雄性大鼠的疼痛性周围神经病变、坐骨神经慢性压迫性损伤 (CCI) 模型中评估 MMP-9 的表达、活性和排泄模式。对 CCI 2 个月过程中的神经样本进行 MMP-9 及其内源性抑制剂、金属蛋白酶组织抑制剂 1 (TIMP-1) 的实时 Taqman RT-PCR，然后对粗神经提取物进行明胶酶谱分析，并使用明胶琼脂糖珠从提取物中纯化 MMP-9。使用 CCI 雌性和雄性大鼠尿液中的蛋白酶活性测定来测定 MMP 排泄。 CCI 后第 1 天神经 MMP-9 表达的最初激增在 CCI 后第 28 天被取代超过 100 倍。晚期神经损伤时MMP-9的高表达伴随着TIMP-1水平的降低。在 CCI 后第 1 天和第 28 天观察到正常神经中不存在 MMP-9，并且存在多种 MMP-9 种类（酶原、成熟酶、同二聚体和异二聚体）。 MMP-9酶原和成熟酶种类在早期和晚期神经损伤中占主导地位，分别与TIMP-1的高表达和低表达水平一致。神经 MMP-9 水平升高与 CCI 后尿液 MMP 排泄升高相对应。所有这些发现在雌性和雄性啮齿动物中都是可比的。本研究为晚期疼痛性周围神经病期间过度的、不受抑制的蛋白水解 MMP-9 活性提供了第一个证据，并表明周围神经损伤后 MMP-9 表达、活性和排泄的模式在两性中是普遍存在的。
In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown. Patterns of MMP-9 expression, activity and excretion were assessed in a model of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI. The initial upsurge in nerve MMP-9 expression at day 1 post-CCI was superseded more than 100-fold at day 28 post-CCI. The high level of MMP-9 expression in late-phase nerve injury was accompanied by the reduction in TIMP-1 level. The absence of MMP-9 in the normal nerve and the presence of multiple MMP-9 species (the proenzyme, mature enzyme, homodimers, and heterodimers) was observed at day 1 and day 28 post-CCI. The MMP-9 proenzyme and mature enzyme species dominated in the early- and late-phase nerve injury, consistent with the high and low level of TIMP-1 expression, respectively. The elevated nerve MMP-9 levels corresponded to the elevated urinary MMP excretion post-CCI. All of these findings were comparable in female and male rodents. The present study offers the first evidence for the excessive, uninhibited proteolytic MMP-9 activity during late-phase painful peripheral neuropathy and suggests that the pattern of MMP-9 expression, activity, and excretion after peripheral nerve injury is universal in both sexes.
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影响因子：
3.7
作者：
Kim Y;Remacle AG;Chernov AV;Liu H;Shubayev I;Lai C;Dolkas J;Shiryaev SA;Golubkov VS;Mizisin AP;Strongin AY;Shubayev VI
通讯作者：
Shubayev VI
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
3.5
作者：
Kobayashi, Hideo;Chattopadhyay, Sharmila;Kato, Kinshi;Dolkas, Jennifer;Kikuchi, Shin-ichi;Myers, Robert R.;Shubayev, Veronica I.
通讯作者：
Shubayev, Veronica I.
影响因子：
--
作者：
Etique N;Verzeaux L;Dedieu S;Emonard H
通讯作者：
Emonard H
影响因子：
15.1
作者：
Chattopadhyay, Sharmila;Myers, Robert R.;Shubayev, Veronica
通讯作者：
Shubayev, Veronica