Objectives:The purpose of the study aims to understand the regeneration process and its cytology mechanism in economic echinoderms.
Materials and Methods:The intestine regeneration process of Apostichopus japonicus was investigated by immunohistochemistry and the cell proliferation was detected by immunofluorescence and flow cytometry. Fibroblast growth factor 4 of A. japonicus (AjFGF4) was screened by RNA-seq analysis and validated to regulate cell proliferation by siAjFGF4 and recombinant-AjFGF4 treatment. The binding and co-localization of AjFGF4 and AjFGFR2 were verified by Co-IP, GST-pull down, and immunofluorescence. Then, the AjFGF4-AjFGFR2-ERK-cell cycle axis was examined by western blot, immunofluorescence, and flow cytometry techniques.
Results:The mesentery was served as the epicenter of intestinal regeneration via activating cell proliferation and other cellular events. Mechanically, AjFGF4mediated cell proliferation was dependent on the binding to its receptor AjFGFR2, and then triggered the conserved ERK-MAPK pathway but not JNK and p38 pathway. The activated ERK-MAPK subsequently mediated the expression of cell cycle regulatory proteins of CDK2, Cyclin A, and Cyclin B to promote cell proliferation.
Conclusions:We provide the first functional evidence that AjFGF4-AjFGFR2-ERKcell cycle axis mediated cell proliferation was the engine for mesentery-derived intestine regeneration in echinoderms.
| INTRODUCTIONDamage to organs or tissues by infection, trauma, aging, diseases, congenital defects, and other injuries causes organ malfunction and is lifethreatening under serious conditions. 1 To maintain, improve, and restore organ functions after injury, one of the most exciting current biomedical research challenges is to decipher the molecular basis of organ regeneration, which is regulated by a series of dynamic and complex processes including the interplay among intracellular and extracellular signals, growth factors, cytokines, and other components. 2 Thus, the explorations of the basic principles and the molecular underpinnings of regeneration have provided a rich biological resource and tools for understanding, building, or repairing complex body parts, which could bring us a step closer to regenerating human organs. [3][4][5] However, the regeneration potentials present a heterogeneous distribution from the lowest to the highest phyla. 6 Adult mammals, in particular humans, are not categorized as regeneration-competent species, with a limited organ regenerative capacity following injury. 2,4 Whereas many lower vertebrates or invertebrates, such as amphibians, fish, and echinoderm possess extraordinary abilities to regenerate missing
