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Fibroblast growth factor 9 promotes kidney cell proliferation via WNT signaling-mediated activation of ANXA4


1 School of Bioengineering, Wuhu Institute of Technology, Wuhu, 241003, China
2 Department of Reproductive Medicine, Liaocheng People’s Hospital, Liaocheng, 252000, China

* Address correspondence to: Hongmin Guo,
# These authors contributed equally to this work

BIOCELL 2021, 45(4), 985-994.


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. FGF9 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 FGF9-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 ANXA4 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 β-catenin or ANXA4 inhibited C57BL/6 cell proliferation. Additionally, the expression of ANXA4 was lower in CTNNB1- 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 ANXA4 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.


Cite This Article

LI, T., SUN, X., LI, N., GUO, H. (2021). Fibroblast growth factor 9 promotes kidney cell proliferation via WNT signaling-mediated activation of ANXA4. BIOCELL, 45(4), 985–994.

This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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