226: FGF4 protects podocytes in diabetic kidney disease

Wang S et al., Nat Commun - This study shows that podocyte-derived FGF4 is reduced in DKD and that recombinant FGF4 preserves podocyte survival and glomerular function in diabetic models via FGFR1-AMPK-FOXO1 signaling. Key terms: FGF4, FGFR1, podocyte, AMPK-FOXO1, diabetic kidney disease. Study Highlights:FGF4 expression is downregulated in kidneys from DKD patients and diabetic mouse models and localizes predominantly to podocytes. Podocyte-specific deletion of Fgf4 worsened albuminuria, reduced GFR, increased oxidative stress and podocyte loss in diabetic mice. Systemic treatment with a non-mitogenic recombinant FGF4 improved glucose in db/db mice, lowered UACR and BUN, reduced fibrosis, ROS and apoptosis, and restored podocyte markers in both T1D and T2D models. The protective effects of rFGF4 require podocyte FGFR1 and downstream AMPK-FOXO1 activity, as Fgfr1, Ampk, or Foxo1 podocyte knockouts abolished rFGF4 benefits. rFGF4 also reversed high glucose–induced injury and promoted nuclear FOXO1 in human podocytes and isolated human glomeruli Conclusion:FGF4 is a podocyte-derived regulator that promotes podocyte survival and mitigates DKD through FGFR1-mediated activation of the AMPK-FOXO1 axis, supporting rFGF4 as a potential therapeutic approach for diabetic kidney disease Music:Enjoy the music based on this article at the end of the episode. First author:Wang S Journal:Nat Commun DOI:10.1038/s41467-025-65978-4 Reference:Wang S, Lou J, Pan B, Zhao M, Li Q, Zhou J, et al. FGF4-FGFR1 signaling promotes podocyte survival and glomerular function to ameliorate diabetic kidney disease in male mice. Nat Commun. 2025;16:10430. https://doi.org/10.1038/s41467-025-65978-4 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/fgf4-podocyte-protects-kidney QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-12. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the scientific content of the transcript, focusing on: DKD context and podocyte injury; FGF4 downregulation and podocyte-specific Fgf4 knockout effects; rFGF4 therapeutic effects in DKD mouse models; FGFR1-AMPK-FOXO1 signaling; human cell data; safety considerations; interactions with losartan and SGLT2 inhibit- transcript topics: DKD and podocyte injury; FGF4 as a podocyte-protective factor; Podocyte-specific Fgf4 knockout model (PKO); Recombinant FGF4 therapy in DKD (db/db and STZ models); FGFR1-AMPK-FOXO1 signaling axis; Human podocyte/glomerulus data and translational relevance QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- DKD downregulates FGF4 in podocytes and correlates with disease severity- Podocyte-specific deletion of Fgf4 worsens DKD outcomes (lower GFR, higher albuminuria, histological damage)- Recombinant FGF4 (rFGF4) protects against DKD in two mouse models (db/db and STZ), reducing kidney injury and fibrosis- FGFR1-AMPK-FOXO1 signaling mediates rFGF4's p...