The TRIM14-KIF1B Axis Drives Renal Injury in Diabetic Nephropathy Through TLR4/NF-κB Pathway Modulation

Background: Diabetic nephropathy (DN), a major contributor to end-stage renal disease, remains poorly understood at the molecular level. While the roles of TRIM proteins in metabolic diseases are emerging, the specific function of Tripartite Motif Containing 14 (TRIM14) in DN and its novel interaction with Kinesin Family Member 1B (KIF1B) have not been explored. This study aims to investigate this uncharted mechanistic axis. Methods: A rat DN model was established using a high-fat diet and streptozotocin injection. Transcriptome sequencing, functional enrichment, and protein-protein interaction (PPI) network analyses were performed to identify key regulatory genes and novel interactions. In vitro, high-glucose-exposed HK-2 cells were used for functional assays. The interaction between TRIM14 and KIF1B was validated by co-immunoprecipitation (Co-IP) and immunofluorescence. TRIM14 expression was also assessed in DN patient blood samples via qPCR. Results: Transcriptomic profiling revealed significant enrichment of immune and metabolic pathways in DN, with TRIM14 emerging as a central regulatory gene. TRIM14 expression was markedly elevated in DN rat kidneys (approximately 2-fold increase, p < 0.001), high-glucose-stimulated HK-2 cells (2-fold increase, p < 0.01), and DN patient blood. Knockdown of TRIM14 significantly mitigated high-glucose-induced apoptosis, oxidative stress, and inflammation in HK-2 cells, partially by suppressing the TLR4/NF-κB pathway. Crucially, PPI analysis and Co-IP confirmed KIF1B as a novel and direct TRIM14 interactor, with TRIM14 positively regulating KIF1B expression and co-localizing in HK-2 cells. Conclusion: We report for the first time that the TRIM14-KIF1B axis acts as a key driver of renal injury in DN. TRIM14 exacerbates tubular epithelial cell damage via KIF1B modulation and TLR4/NF-κB activation. TRIM14 represents a promising diagnostic biomarker and therapeutic target for DN.