Disrupted Alternative Splicing of RAB11FIP3 Contributes to Diabetic Foot Ulcer Dysfunction.

ABSTRACT: Dysregulation of alternative splicing (AS) has been associated with various complications of diabetes, yet its role in the pathogenesis of diabetic foot ulcers (DFUs) and its involvement in metabolic memory (MM) remain unclear. In this study, we identified specific AS events in RAB11FIP3, notably the full-length (RAB11FIP3-FL) isoform and exon 6 exclusion (RAB11FIP3-Δ6). We found that RAB11FIP3 (FL/Δ6) ratio is significantly elevated in patients with MM and DFUs. Additionally, we demonstrated that knockdown of RAB11FIP3-FL alleviates vascular endothelial damage associated with MM and enhances DFU healing. Furthermore, we identified that HNRNPL promotes the retention of exon 6 in RAB11FIP3-FL, thereby increasing the FL/Δ6 ratio. Mechanistically, our results show that RAB11FIP3-FL promotes t

SUBMITTER: Zhu D 

PROVIDER: S-EPMC12320866 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature