Abstract: SA-PO132
The Role of PCSK9 on the Glomerular Lipid Accumulation and Renal Injury in the Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Park, Jimin, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Nam, Boyoung, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Kang, Sukyung, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Choi, Arum, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Wu, Meiyan, The First Hospital of Jilin University, Changchun, China
- Han, Seung Hyeok, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
- Yoo, Tae-Hyun, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
Background
Glomerular lipid accumulation is one of the pathologic characteristics of diabetic kidney disease (DKD). Recent evidences suggested that proprotein convertase subtilisin kexin type 9 (PCSK9) has a particular effect on the cellular lipid homeostasis. We aimed to evaluate the role of PCSK9 on the lipid accumulation in glomeruli and podocyte under the diabetic conditions.
Methods
C57BL/6 and PCSK9 knockout (KO) mice were maintained with high fat diet for 12 weeks with low dose streptozocin intraperitoneal injection. Urinary albumin-to-creatinine ratio (ACR), total cholesterol and triglyceride in kidney tissues were measured. BODIPY 493/503 staining was performed for evaluating lipid accumulation in the kidney. Foot process effacement in glomeruli was evaluated by standard transmission electron microscopy. In vitro study, mouse podocytes were stimulated with TNF-α and palmitic acid, and PCSK9 was up- or down-regulated by overexpressing lenti virus or siRNA. Apoptosis, mitochondrial morphology and energy metabolic key enzymes were evaluated both in vivo and vitro.
Results
Blood glucose and serum cholesterol were significantly increased, and urinary ACR and foot process effacement were increased in diabetic mice and these changes were exaggerated in the PCSK9 KO mouse with diabetes. Cholesterol and triglyceride levels in the kidney tissues were higher in PCSK KO mice with diabetes than those in control and diabetic mice. Mitochondrial morphology and the expression of energy metabolic enzymes were disturbed in the kidneys of diabetic PCSK KO mice. In vitro, the intracellular lipid contents was increased and apoptosis combined with mitochondrial swelling and crista disruption were also increased in podotyes with TNF-α and palmitic acid stimuli. All of these changes were ameliorated through mPCSK9 overexpression and aggravated by PCSK9 siRNA treatment.
Conclusion
These findings suggest that PCSK9 down-regulation in the podocytes is involved in lipid accumulation and consequent mitochondrial dysfunction and apoptosis in the DKD.