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

[摘要] 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.

[学科分类] 仪器

[关键词] Fibroblast growth factor;Kidney cell;Proliferation;ANXA4;WNT