Abstract: SA-PO0313
TIF1γ Activates the Apelin-APJ-Sirt3 Axis to Restore Kidney and Skeletal Muscle Homeostasis in Diabetic Mice
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Lee, Seunghye, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Jeon, Hyejin, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Kim, Jin Hyun, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Jung, Sehyun, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Jang, Hani, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Chang, Se-Ho, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
- Kim, Hyun-Jung, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea (the Republic of)
Background
The Apelin–APJ signaling axis plays a crucial role in cardiovascular and renal physiology, exerting anti-inflammatory, anti-fibrotic, and metabolic regulatory effects. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, is also essential for renal energy homeostasis. We reported that TIF1g improved renal histopathology and skeletal muscle function in diabetic mice. However, the underlying molecular mechanisms remain unclear. We investigated if TIF1g activates the Apelin–APJ–Sirt3 axis to restore renal and muscle homeostasis under diabetic stress.
Methods
Mice were assigned to four groups: db/m+ mice (non-diabetic, normal mice), db/db mice (untreated mice), and db/db mice treated with CMV-TIF1g or TGF-b-TIF1g-plasmids. The plasmids (40 mg/mouse) were administered intraperitoneally once weekly for 16 weeks, and blood, kidney, and skeletal muscle tissues were harvested. Human renal tubular epithelial cells (HK-2) were exposed to metabolic stimuli to assess changes in Apelin, APJ, and Sirt3 expression. C2C12 myoblasts were transfected with CMV/TGF-b primer-driven TIF1g-encoding plasmids using lipofectamine, and conditioned media (CM) were applied to HK-2 cells with metabolic stimuli.
Results
TIF1γ plasmid administration restored renal and skeletal muscle Apelin and Sirt3 expression and reduced APJ expression in db/db mice. Metabolic stress decreased Apelin and Sirt3 expression and increased APJ expression in HK-2 cells. TIF1g overexpression in C2C12 cells increased Apelin and Sirt3 expression and reduced APJ expression under lipotoxic conditions. In TIF1g-transfected C2C12 cells, apelin secretion was elevated. CM from TIF1g-transfected C2C12 cells attenuated EMT in palmitate-treated HK-2 cells, compared to medium from non-transfected C2C12 cells. Conversely, apelin knockdown in C2C12 cells accelerated EMT in palmitate-treated HK-2 cells, as evidenced by decreased bone morphogenetic protein-7 and increased EMT-related factors compared to palmitate alone and knockdown control.
Conclusion
Our findings emphasize that TIF1g might be a multi-targeted therapeutic agent for diabetic kidney disease, mitigating both renal and muscular complications and TIF1g is involved in activation of Apelin–APJ–Sirt3 axis to improve kidney and muscle pathology and function in metabolic stress conditions.