Extracellular ADP regulates lesion-induced in vivo cell proliferation and death in the zebrafish retina
Extracellular ADP regulates lesion-induced in vivo cell proliferation and death in the zebrafish retina
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DOI：
10.1111/j.1471-4159.2009.06352.x
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发表时间：
2009-10-01
影响因子：
4.7
通讯作者：
Paula Faillace, Maria
中科院分区：
文献类型：
--
作者：
Battista, Ariadna G.;Jimena Ricatti, Maria;Paula Faillace, Maria
成体硬骨视网膜通过神经发生的再生和生长有助于确定细胞增殖和分化的分子和细胞机制。在这篇报道中，我们证明了内源性嘌呤能信号调节成年斑马鱼视网膜细胞毒性损伤所诱导的细胞增殖，主要是损伤视网膜内层。特别是，我们发现，在再生过程的退行性和增殖期，ADP而不是ATP或腺苷显著促进了细胞分裂，如损伤后5-溴-2‘-脱氧尿苷掺入所评估的那样。如眼内注射选择性拮抗剂所显示的那样，ADP的这种作用是通过P2Y1代谢性受体实现的。此外，我们描述了嘌呤能信号在调节损伤诱导的细胞死亡中的作用。清除细胞外核苷酸显着增加细胞死亡，主要见于视网膜内层。这种作用是通过阻断P2Y1受体来部分再现的，这表明ADP具有神经保护功能，ADP来自细胞外ATP，可能是哇巴因治疗导致濒死细胞释放的。这项研究证明了ADP作为旁分泌信号在视网膜组织损伤修复中的关键作用。
Regeneration and growth that occur in the adult teleost retina by neurogenesis have been helpful in identifying molecular and cellular mechanisms underlying cell proliferation and differentiation. In this report, we demonstrate that endogenous purinergic signals regulate cell proliferation induced by a cytotoxic injury of the adult zebrafish retina which mainly damages inner retinal layers. Particularly, we found that ADP but not ATP or adenosine significantly enhanced cell division as assessed by 5-bromo-2'-deoxyuridine incorporation following injury, during the degenerative and proliferative phase of the regeneration process. This effect of ADP occurs via P2Y1 metabotropic receptors as shown by intra-ocular injection of selective antagonists. Additionally, we describe a role for purinergic signals in regulating cell death induced by injury. Scavenging of extracellular nucleotides significantly increased cell death principally seen in the inner retinal layers. This effect is partially reproduced by blocking P2Y1 receptors suggesting a neuroprotective function for ADP, which is derived from extracellular ATP probably released by dying cells as a consequence of the ouabain treatment. This study demonstrates a crucial role for ADP as a paracrine signal in the repair of retinal tissue following injury.