@Article{biocell.2021.012371,
AUTHOR = {TING LI, XINHUI SUN, NANNAN LI, HONGMIN GUO},
TITLE = {Fibroblast growth factor 9 promotes kidney cell proliferation via WNT signaling-mediated activation of <i>ANXA4</i>},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {4},
PAGES = {985--994},
URL = {http://www.techscience.com/biocell/v45n4/42352},
ISSN = {1667-5746},
ABSTRACT = {Fibroblast growth factors (FGFs) play pivotal roles in cell migration and proliferation. However, the identity of
the FGF that plays a dominant role in kidney cell proliferation remains unclear. Therefore, in this study, we investigated
the dominant FGF among all FGFs. To this end, RNA-sequencing, qRT-PCR, western blotting, and ChIP assays were
performed. <i>FGF9</i> showed the highest expression among all FGFs, and its overexpression significantly promoted
proliferation in the mouse kidney cell line C57BL/6 and increased JNK and AKT phosphorylation levels. Further,
RNA-seq analysis identified 365 upregulated and 276 downregulated genes in <i>FGF9</i>-overexpressed cells. These
differentially expressed genes were classified primarily into 20 biological pathways and were enriched in 31 gene
ontology terms. qRT-PCR revealed that the expression of WNT and NF-κB signaling genes, as well as <i>ANXA4</i>
expression patterns, correlated with the RNA-seq data, while FGF9-overexpressed cells accumulated more β-catenin, a
key WNT signaling protein, compared to control cells. Moreover, downregulation of the gene that encodes <i>β-catenin</i>
or <i>ANXA4</i> inhibited C57BL/6 cell proliferation. Additionally, the expression of <i>ANXA4</i> was lower in <i>CTNNB1</i>-
knockdown cells than in the control group. Additionally, the ChIP assay revealed that a transcription factor complex
containing TCF4 and β-catenin directly binds to the <i>ANXA4</i> promoter. Taken together, these results suggest a role of
FGF9 in the regulation of kidney cell migration. These findings may prove useful in the development of future therapies.},
DOI = {10.32604/biocell.2021.012371}
}