Alternative Splicing for Activation of Coagulation Factor XIII-A in the Fish Retina After Optic Nerve Injury.
Alternative Splicing for Activation of Coagulation Factor XIII-A in the Fish Retina After Optic Nerve Injury.
复制标题
视神经损伤后鱼视网膜中凝血因子 XIII-A 的选择性剪接激活。
DOI：
10.1007/978-3-319-75402-4_48
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Kato S.
中科院分区：
文献类型：
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作者：
Sugitani K;Koriyama Y;Ogai K;Furukawa A;Kato S.
因子XIII-A（FXIII-A），已被称为细胞转氨酶，在介导各种组织中的交联反应中起重要作用。FXIII-A作为视神经损伤后鱼视网膜和视神经中的再生分子之一，并在几小时内在损伤部位被激活。先前的研究已经表明，激活的FXIII-A诱导神经突从受损的视网膜神经节细胞中长出，并支持再生视神经的伸长。然而，FXIII-A的激活机制仍然未知。此外，损伤的组织不表达凝血酶，一种已知的血浆FXIII的激活剂。在这里，我们研究了基于两个不同区域的FXIII-A的mRNA表达，一个区域编码激活肽，另一个区域编码酶活性位点。我们发现，与编码活性位点的区域相比，编码活化肽的区域的表达被显著抑制。一个短型FXIII-A的cDNA缺乏激活肽的过表达研究显示，与全长FXIII-A的cDNA相比，在鱼视网膜外植体培养诱导长的神经突生长。目前的研究结果表明，选择性剪接可能发生在FXIII-A基因，导致缺失的区域编码的激活肽，从而允许直接生产的激活FXIII-A蛋白在鱼视网膜和视神经损伤后的视神经。
Factor XIII-A (FXIII-A), which has become known as cellular transglutaminase, plays important roles in mediating cross-linking reactions in various tissues. FXIII-A acts as one of the regeneration molecules in the fish retina and optic nerve after optic nerve injury and becomes activated at the site of injury within a few hours. Previous research has shown that activated FXIII-A induces neurite outgrowth from injured retinal ganglion cells and supports elongation of the regenerating optic nerve. However, the activation mechanism of FXIII-A remains unknown. Furthermore, the injured tissues do not express thrombin, a known activator of plasma FXIII. Here, we investigated the mRNA expression of FXIII-A based on two different regions, one encoding the activation peptide and the other encoding the enzymatic active site. We found that expression of the region encoding the activation peptide was markedly suppressed compared with the region encoding the active site. An overexpression study with a short-type FXIII-A cDNA lacking the activation peptide revealed induction of long neurite outgrowth in fish retinal explant cultures compared with full-length FXIII-A cDNA. The present findings suggest that alternative splicing may occur in the FXIII-A gene, resulting in deletion of the region encoding the activation peptide and thus allowing direct production of activated FXIII-A protein in the fish retina and optic nerve after optic nerve injury.