当前位置： SCI文献检索 > DEVELOPMENTAL BIOLOGY期刊下所有文献 > Insights into intestinal regeneration signaling mechanisms.

Insights into intestinal regeneration signaling mechanisms.

Abstract：

:The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestinal regenerative stages, suggesting that the Wnt/β-catenin pathway is active during this process. Here, we used small molecules, putative disruptors of the Wnt pathway, to determine the potential role of the canonical Wnt pathway on intestine regeneration in the sea cucumber Holothuria glaberrima. We evaluated their effects in vivo by using histological analyses for cell dedifferentiation, cell proliferation and apoptosis. We found that iCRT14, an alleged Wnt pathway inhibitor, decreased the size of the regenerating intestine, while LiCl, a presumed Wnt pathway activator, increased its size. The possible cellular mechanisms by which signaling pathway disruptors affect the gut rudiment size were further studied in vitro, using cultures of tissue explants and additional pharmacological agents. Among the tested signaling activators, those that act through GSK-3 inhibition, LiCl, 1-Azakenpaullone, and CHIR99021 were found to increase muscle cell dedifferentiation, while the inhibitor iCRT14 blocked cell dedifferentiation. Differently, cell proliferation was reduced by all GSK-3 inhibitors, as well as by iCRT14 and C59, which interferes with Wnt ligand secretion. The in vivo temporal and spatial pattern of β-catenin activity was determined using an antibody against phosphorylated β-catenin and shown to correlate with cell proliferative activity. In vitro treatment using C59 decreased the number of cells immunostained for nuclear phosphorylated β-catenin. Our results showed that the cell dedifferentiation observed during intestinal regeneration can be decoupled from the cell proliferation event and that these cellular processes can be modulated by particular signaling pathway inhibitors and activators. These results open the door for future studies where the cellular signaling pathways involved at each regeneration stage can be determined.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Bello SA,Torres-Gutiérrez V,Rodríguez-Flores EJ,Toledo-Román EJ,Rodríguez N,Díaz-Díaz LM,Vázquez-Figueroa LD,Cuesta JM,Grillo-Alvarado V,Amador A,Reyes-Rivera J,García-Arrarás JE

doi

10.1016/j.ydbio.2019.10.005

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

12-31

issue

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(18)30503-7

journal_volume

458

pub_type

杂志文章

在线工具

Insights into intestinal regeneration signaling mechanisms.