Abstract: PO0898
UCP2 Activates Autophagy to Protect Against Albuminuria and Podocyte Injury in Diabetes
Session Information
- Diabetic Kidney Disease: Basic Mechanisms
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Yang, Qianqian, Second Affiliate Hospital of Nanjing Medical Univerity, Nanjing, Jiangsu, China
- Sun, Qi, Second Affiliate Hospital of Nanjing Medical Univerity, Nanjing, Jiangsu, China
- Yang, Junwei, Second Affiliate Hospital of Nanjing Medical Univerity, Nanjing, Jiangsu, China
Background
Podocytes injury and albuminuria are leading features of glomerular damage in diabetic kidney disease. Autophagy plays an important role in maintaining podocyte homeostasis. However, the underlying mechanism remains unknown. In this study, we reported a critical role of mitochondrial uncoupling protein 2 (UCP2) in maintaining autophagic activity and protecting podocyte from hyperglycemia-induced injury.
Methods
First, to elucidate the role of UCP2 in podocyte homeostasis and injury in vivo, we generated conditional knockout mice in which UCP2 is specifically ablated in podocytes by using Cre–LoxP recombination system. Second, autophagosome was detected by transmission electron microscopy. Dual-fluorescence lentiviral mRFP-GFP-LC3 was transfected into podocyte to detect the autophagic flux. Autophagy marker, LC3II, p62 and Beclin1, were tested by quantitative real-time PCR and western blot. At last, AMPK activator and mTORC1 inhibitor were used to identify the signaling pathway UCP2-mediated to regulate autophagy.
Results
UCP2 was upregulated synchronously with autophagy marker during glomerular development. Loss of UCP2 in podocytes led to a decrease of autophagic activity and an increase of podocyte injury. Podocyte-specific knockout of UCP2 aggravated age-related proteinuria and increased podocyte susceptibility to hyperglycemia in streptozotocin (STZ) -induced DKD mice. UCP2 promotes podocyte autophagy through activation of AMPK/mTOR signaling pathway.
Conclusion
Our findings demonstrates a critical protective role of UCP2 in podocyte survival via maintaining autophagic activity through AMPK/mTOR signaling pathway.
Funding
- Government Support - Non-U.S.