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During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.
Preparing your E-Poster
Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.
E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
Please follow the instructions below to input your abstract title.
Abstract titles should be brief and reflect the content of the abstract.
Chronic kidney disease (CKD) is a global health burden, with ineffective therapies leading to increasing morbidity and mortality. Renal interstitial fibrosis is a common pathway in advanced CKD, resulting in kidney function and structure deterioration. FTO, the m6A demethylase, has been demonstrated to promote renal fibrosis by targeting RUNX1 mRNA and increasing its stability in our previous study. In this study, we aim to elucidate the mechanism mediating FTO upregulation and the potential pathway involved in the FTO-RUNX1 axis during renal fibrosis.
UUO (unilateral ureteral obstruction) was implicated to induce renal fibrosis in vivo, and HK-2 cells were treated with TGF-β1 (5ng/ml) in vitro. Western blot was used to detect the expression of the targeted proteins and IP-WB was used for testing the histone lactylation of FTO. Merip-qPCR and Actinomycin assay were applied to exam the RUNX1-specific m6A modification and the mRNA stability. Differential gene and enrichment pathway were analyzed based on R software.
FTO and IGF2BP3 were significantly up-regulated during the development renal fibrosis both in vivo and in vitro, and TGF-β1 upregulated the histone lactylation of FTO in HK-2 cells. FTO knockdown significantly enriched the m6A modification of RUNX1 mRNA and promoted its degradation. KEGG enrichment was analyzed based on the UUO mouse model sequencing, and PI3K/AKT pathway was dramatically increased compared to the sham group. We further demonstrated that FTO knockdown inhibited the upregulation of PI3K/AKT pathway in UUO mouse model in vivo, and in TGF-β1 treated HK-2 cells in vitro. At last, we detected the autophagy flux and the main inflammatory factors in WT and FTO+/- mice, and found which indicated that FTO knockdown promoted the conversion from LC3-I to LC3-II, as well as and partially promoted the degradation of the autophagy substrate protein p62, suggesting enhanced autophagy induction due to FTO deletion. Meanwhile, qRT-PCR showed FTO knockdown partially attenuated the upregulation of chemokine MCP-1 and pro-inflammatory mediator (TNF-α and IL-6) induced by UUO treatment in vivo and TGF-β1 treatment in HK-2 cells.
In this study, we provided mechanistic insights into the role of FTO lactylation in renal fibrosis. Our data revealed that FTO upregulation promoted renal fibrosis by activating RUNX1-PI3K/AKT pathway via m6A -IGF2BP3 manner, which indicated that inhibiting lactylation of FTO or restraining RUNX1-PI3K/AKT might be a promising therapeutic strategy for retarding CKD progression.
