Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Av. Diagonal 643, 08028, Barcelona, Spain.
Sci Rep. 2021 Jan 13;11(1):881. doi: 10.1038/s41598-020-79588-1.
Despite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically HO, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or HO have the potential to rescue regeneration after MEK-inhibition, either by HO-treatment or light therapy, (2) ROS and/or HO are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.
尽管人们对控制模型生物再生过程的分子途径进行了广泛的研究，但对于诱导再生所需的实际起始信号知之甚少。最近，ERK 信号的激活已被证明是扁形动物再生所必需的。然而，ERK 信号是如何被激活的仍然未知。活性氧（ROS）是几种模型中再生所必需的早期信号，包括扁形动物。然而，ROS 和 MAPK/ERK 之间可能的相互作用尚未被描述。在这里，通过干扰主要介质（ROS、EGFR 和 MAPK/ERK），我们能够识别出创伤诱导的 ROS，特别是 HO，作为再生激活的上游线索。我们的数据表明，在最早的再生阶段，与再生相关的 ROS 产生和 MAPK/ERK 激活之间存在新的关系，以及 EGFR 信号通路的参与。我们的结果表明：（1）ROS 和/或 HO 有可能在 MEK 抑制后通过 HO 处理或光疗来挽救再生，（2）ROS 和/或 HO 是激活 MAPK/ERK 信号通路所必需的，（3）在扁形动物再生过程中，EGFR 途径可以介导 ROS 的产生和 MAPK/ERK 的激活。
