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Cell Prolif
2023 Feb 01;562:e13351. doi: 10.1111/cpr.13351.
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Mesentery AjFGF4-AjFGFR2-ERK pathway modulates intestinal regeneration via targeting cell cycle in echinoderms.
Zeng C
,
Guo M
,
Xiang Y
,
Song M
,
Xiao K
,
Li C
.
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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, AjFGF4-mediated 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-ERK-cell cycle axis mediated cell proliferation was the engine for mesentery-derived intestine regeneration in echinoderms.
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