Saito Yuichi, Yamaguchi Akihiro, Nakamura Shinsuke, Okuyoshi Hiroyuki, Shimazawa Masamitsu, Hara Hideaki
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Neurosci Lett. 2020 May 14;727:134930. doi: 10.1016/j.neulet.2020.134930. Epub 2020 Apr 3.
Accumulated evidence indicates that platelet-derived growth factor (PDGF) contributes to various types of tissue regeneration. However, the effects and mechanisms of PDGF signaling for retina regeneration have not been sufficiently investigated. To clarify this, we investigated the role of PDGF signaling in retina regeneration process after needle puncture in zebrafish. Time-course analysis showed a spike peak of pdgf-a at 6 h after injury and a broad peak of pdgf-b during 6-96 h after injury. Inhibition of PDGF signaling with AG1295 suppressed BrdU-positive proliferative cell numbers at 4 days after injury. At the same time, retina regeneration-associated transcription factors, ascl1a and pax6b, were down-regulated by AG1295 treatment. Intravitreal injection of human recombinant PDGF-AA or -BB into intact zebrafish induced the cell proliferation. PDGF-BB injection induced the Müller glia-derived neurogenic cluster; PDGF-AA increased the 4C4-positive microglia. These findings indicate that PDGF signaling contributes to retina regeneration in zebrafish and causes different types of cell proliferation, depending on each subtype of PDGF. (160 words).
越来越多的证据表明，血小板衍生生长因子（PDGF）有助于多种类型的组织再生。然而，PDGF信号通路对视网膜再生的影响及机制尚未得到充分研究。为阐明这一点，我们研究了斑马鱼针刺损伤后PDGF信号通路在视网膜再生过程中的作用。时间进程分析显示，损伤后6小时pdgf-a出现尖峰，损伤后6 - 96小时pdgf-b出现宽峰。用AG1295抑制PDGF信号通路可抑制损伤后4天BrdU阳性增殖细胞数量。同时，AG1295处理下调了视网膜再生相关转录因子ascl1a和pax6b。向完整的斑马鱼玻璃体内注射人重组PDGF - AA或 - BB可诱导细胞增殖。注射PDGF - BB可诱导穆勒胶质细胞源性神经源性簇；注射PDGF - AA可增加4C4阳性小胶质细胞。这些发现表明，PDGF信号通路有助于斑马鱼视网膜再生，并根据PDGF的各亚型导致不同类型的细胞增殖。 （160字）
