Open Access

ARTICLE

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

TING LI^1,#, XINHUI SUN^2,#, NANNAN LI¹, HONGMIN GUO^2,*

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. https://doi.org/10.32604/biocell.2021.012371

Received 28 June 2020; Accepted 23 December 2020; Issue published 22 April 2021

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. 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.

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