Ivanova Anastasiya S, Shandarin Igor N, Ermakova Galina V, Minin Andrey A, Tereshina Maria B, Zaraisky Andrey G
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia.
Sci Rep. 2015 Jan 29;5:8123. doi: 10.1038/srep08123.
Agr family includes three groups of genes, Ag1, Agr2 and Agr3, which encode the thioredoxin domain-containing secreted proteins and have been shown recently to participate in regeneration of the amputated body appendages in amphibians. By contrast, higher vertebrates have only Agr2 and Agr3, but lack Ag1, and have low ability to regenerate the body appendages. Thus, one may hypothesize that loss of Ag1 in evolution could be an important event that led to a decline of the regenerative capacity in higher vertebrates. To test this, we have studied now the expression and role of Ag1 in the regeneration of fins of a representative of another large group of lower vertebrates, the fish Danio rerio. As a result, we have demonstrated that amputation of the Danio fins, like amputation of the body appendages in amphibians, elicits an increase of Ag1 expression in cells of the stump. Furthermore, down-regulation of DAg1 by injections of Vivo-morpholino antisense oligonucleotides resulted in a retardation of the fin regeneration. These data are in a good agreement with the assumption that the loss of Ag1 in higher vertebrates ancestors could lead to the reduction of the regenerative capacity in their modern descendants.
Agr家族包括三组基因，即Ag1、Agr2和Agr3，它们编码含硫氧还蛋白结构域的分泌蛋白，最近已被证明参与两栖动物肢体截断后的再生过程。相比之下，高等脊椎动物只有Agr2和Agr3，而缺乏Ag1，并且肢体再生能力较低。因此，可以推测在进化过程中Ag1的缺失可能是导致高等脊椎动物再生能力下降的一个重要事件。为了验证这一点，我们现在研究了Ag1在另一大类低等脊椎动物——斑马鱼鳍再生中的表达和作用。结果表明，斑马鱼鳍的截断，与两栖动物肢体的截断一样，会引发残端细胞中Ag1表达的增加。此外，通过注射活体吗啉代反义寡核苷酸下调DAg1会导致鳍再生延迟。这些数据与以下假设高度一致：高等脊椎动物祖先中Ag1的缺失可能导致其现代后代再生能力的降低。
