| First Author | Yang Q | Year | 2023 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1869 |
| Issue | 5 | Pages | 166705 |
| PubMed ID | 37023910 | Mgi Jnum | J:335245 |
| Mgi Id | MGI:7468358 | Doi | 10.1016/j.bbadis.2023.166705 |
| Citation | Yang Q, et al. (2023) UCP2 deficiency impairs podocyte autophagy in diabetic nephropathy. Biochim Biophys Acta Mol Basis Dis 1869(5):166705 |
| abstractText | OBJECTIVE: Podocytes have been indicated to be a critical factor for the development of diabetic kidney disease. Podocyte loss leads to irreversible glomerular injury and proteinuria in animal models. As terminal differentiated cells, autophagy is crucial for maintaining podocyte homeostasis. Previous studies have shown that Uncoupling proteins 2 (UCP2) regulate fatty acid metabolism, mitochondrial calcium uptake and reactive oxygen species (ROS) production. This study aimed to investigate whether UCP2 promote autophagy in podocyte and further explore the regulation mechanism of UCP2. METHODS: For podocyte-specific UCP2-KO mice, we cross bred UCP2f(l/fl) mouse strain with the podocin-Cre mice. Diabetic mice were obtained by daily intraperitoneally injections of 40 mg/kg streptozotocin for 3 days. After 6 weeks, mice were scarified, and kidney tissues were analyzed by histological stain, Western blot, Immunofluorescence, and immunohistochemistry. Also, urine samples were collected for protein quantification. For in vitro study, podocytes were primary cultured from UCP2f(l/fl) mouse or transfected with adeno-associated virus (AAV)-UCP2. RESULTS: Diabetic kidney showed elevated expression of UCP2 and specific ablation of UCP2 in podocyte aggravates diabetes-induced albuminuria and glomerulopathy. UCP2 protects hyperglycemia-induced podocyte injury by promoting autophagy in vivo and in vitro. Rapamycin treatment significantly ameliorates streptozotocin (STZ)-induced podocyte injury in UCP2(-/-) mice. CONCLUSION: UCP2 expression in podocyte increased under diabetic condition and appeared to be an initial compensatory response. UCP2 deficiency in podocyte impaired autophagy and exacerbates podocyte injury and proteinuria in diabetic nephropathy. |
