Back
For best output, select "Paper Size" as "A4" and "Margin" as "0" or "None".
To save or print to PDF, please select Print Destination > Save as PDF, enable Background Graphics under "More Settings", then click "Save".
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.
Recent research indicates that formononetin exhibits potent anti-inflammatory effects in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. This study aimed to investigate the therapeutic effects of formononetin on ischemia/reperfusion-induced AKI (IRI-AKI) and elucidate the underlying mechanisms.
We employed an IRI-AKI mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation in AKI. Mice were pretreated with formononetin (12.5, 25, or 50 mg/kg/day) for 7 days before IRI modeling. In vitro experiments utilized BMDMs stimulated with LPS and IFN-γ, treated with formononetin (10, 20, or 40 μM), and transfected with KLF6 overexpression plasmid to explore the molecular mechanisms.
Formononetin administration significantly preserved kidney function, as evidenced by reduced serum creatinine and blood urea nitrogen levels compared to untreated IRI-AKI mice. Histological examination revealed less pathological damage to renal tubules, with reduced inflammatory cell infiltration, tubular dilation, and vacuolar degeneration. Immunohistochemistry and molecular analysis confirmed decreased expression of tubular injury markers KIM-1 and NGAL at both mRNA and protein levels in formononetin-treated groups. Furthermore, formononetin effectively suppressed the expression and secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and MCP-1) in both kidney tissue and serum. Immunofluorescence and immunohistochemical staining demonstrated significantly reduced expression of inflammatory factors in kidney tissue, accompanied by decreased F4/80-positive macrophage infiltration. In vitro studies revealed that formononetin dose-dependently inhibited macrophage polarization toward the pro-inflammatory phenotype in LPS and IFN-γ-stimulated BMDMs. This was characterized by reduced expression of CD86 and iNOS, decreased TNF-α levels, and a lower proportion of CD86-positive cells as confirmed by flow cytometry (over 97% F4/80⁺CD11b⁺ macrophages). Mechanistically, immunofluorescence staining showed that formononetin reduced KLF6 expression in F4/80-positive macrophages in kidney tissue. In BMDMs, formononetin significantly inhibited both KLF6 expression and STAT3 phosphorylation. Critically, overexpression of KLF6 abolished formononetin's inhibitory effects on pro-inflammatory cytokine production, CD86 and iNOS expression, and STAT3 phosphorylation, confirming the essential role of the KLF6/STAT3 pathway.
Our findings demonstrate that formononetin significantly improves renal function and reduces inflammation in IRI-AKI by inhibiting KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a promising therapeutic option for the treatment of IRI-AKI and highlights the KLF6/STAT3 pathway as a potential therapeutic target for modulating macrophage-driven inflammation in kidney injury.
