Genotype and Injury Effect on the Expression of a Novel Hypothalamic Protein Sushi Repeat-Containing Protein X-Linked 2 (SRPX2)
Genotype and Injury Effect on the Expression of a Novel Hypothalamic Protein Sushi Repeat-Containing Protein X-Linked 2 (SRPX2)
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DOI：
10.1016/j.neuroscience.2019.07.040
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发表时间：
2019-09-01
期刊：
影响因子：
3.3
通讯作者：
Pitkanen, Asla
中科院分区：
文献类型：
--
作者：
Anwer, Mehwish;Bolkvadze, Tamuna;Pitkanen, Asla
SRPX2是一种新型下丘脑蛋白，是尿激酶型纤溶酶原激活物受体（uPAR）的配体，在脑损伤后细胞外基质的蛋白水解和组织重塑中起重要作用。然而，对SRPX2的调控知之甚少。我们的目的是研究SRPX2的表达是否会因(i) uPAR或uPA（尿激酶型纤溶酶原激活剂）的缺乏和（ii）创伤性脑损伤（TBI）而改变。SRPX2在野生型（Wt）、Plaur(-/-) （upar缺陷）和Plaur(-/-) （upa缺陷）小鼠中进行表达评估，这些小鼠有和没有控制性皮质撞击损伤（CCI）。下丘脑SRPX2+神经元数量与Plau（-/-）小鼠（2985 +/- 138 vs. 2890 +/- 92, p > 0.05）和Plau（-/-）小鼠（2180 +/- 232 vs. 2027 +/- 77, p > 0.05）的Wt窝代相当。Wt-CCI组下丘脑SRPX2+神经元数量与对照组相当（3645 +/- 288 vs. 3385 +/- 192, p < 0.05）。脑外伤后下丘脑、海马和丘脑Srpx2基因表达未发生改变。然而，在tbi后4天，Srpx2基因在Plau(-/-) CCI小鼠的病变周围皮层中的表达上调，达到假手术组的123% （p < 0.05）。使用SRPX2表达的无监督分层聚类不能识别基因型或损伤特异性聚类。我们的数据表明，SRPX2在下丘脑中的表达可以抵抗尿激酶系统中的遗传缺陷或影响下丘脑的TBI。然而，Srpx2基因在脑损伤后的恢复过程中表达升高的作用还有待进一步探讨。(c) 2019 ibroElsevier Ltd.出版。版权所有。
Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel hypothalamic protein and a ligand of the urokinase-type plasminogen activator receptor (uPAR), which is essential for proteolysis of extracellular matrix and tissue remodeling after an insult to the brain. However, little is known about regulation of SRPX2. Our objective was to investigate if SRPX2 expression is altered by (i) the deficiency of uPAR or uPA (urokinase-type plasminogen activator), and (ii) traumatic brain injury (TBI). SRPX2 expression was assessed in wild type (Wt), Plaur(-/-) (uPAR-deficient), and Plaur(-/-) (uPA-deficient) mice, with and without controlled cortical impact injury (CCI). The number of SRPX2+ neurons in hypothalamus was comparable to that in Wt littermates in Plaur(-/-) (2985 +/- 138 vs. 2890 +/- 92, p > 0.05) and Plau(-/-) mice (2180 +/- 232 vs. 2027 +/- 77, p > 0.05). The number of hypothalamic SRPX2+ neurons in the Wt-CCI group was comparable to that in controls (3645 +/- 288 vs. 3385 +/- 192, p > 0.05). Hypothalamic, hippocampal and thalamic Srpx2 gene expression was unaltered after TBI. However, at 4 days post-TBI Srpx2 gene expression was upregulated in the perilesional cortex of Plau(-/-) CCI mice up to 123% of that in the sham group (p < 0.05). Unsupervised hierarchical clustering using SRPX2 expression did not identify genotype or injury-specific clusters. Our data demonstrate that SRPX2 expression in the hypothalamus is resistant to genetic deficiencies in the urokinasesystem or to the hypothalamus-affecting TBI. The contribution of elevated Srpx2 gene expression in perilesional cortex to post-TBI recovery process, however, requires further exploration. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.