Abstract: SA-PO1160
Nano Delivery of Sinomenine Targeting Mitochondria to Improve Mitochondrial Autophagy against Kidney Fibrosis through PINK1/Parkin Pathway
Session Information
- CKD: Mechanisms - 3
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Author
- Huang, Hong Dong, Capital Medical University, Beijing, China
Background
Mitophagy plays a key role in maintaining kidney function and impaired in pathologic states.This study investigated the protective effect of mitochondria-targeted nano sinomenine on renal fibrosis and its molecular mechanism.
Methods
Synthesis mitochondria-targeting nanomaterials. Cell fibrosis cell and animal model were established. Different concentrations of nano sinomenine were used to interfere with cell fibrosis and animal model. Western blot/ flow cytometry were used to detect the expression of LC3, CollagenI, α-SMA and ROS.The expression of PINK1/Parkin were analyzed by RNA-SEQ. The mitochondria and autophagosomes of mitochondria-like organelles were observed by electron microscope. Western blot and immunofluorescence were used to compare the expressions of fibrotic proteins CollagenI, α-SMA, Fibronectin, and mitochondrial autophagy in renal tissues of mice in each group. The renal tubule boundary destruction, atrophy and collagen deposition were observed by PAS and Masson staining.
Results
Nanometer sinomenine targeting mitochondria was successfully established.Cell experiments induced by TGF-β1 and animal experiments on adenine and UUO surgical models confirmed that mitochondrial autophagy was enhanced and TGF-β1 was decreased in the group treated with nano sinomenine. Nano sinomenine decreased the expression of CollagenI, α-SMA, Fibronectin proteins. PINK1 was highly enriched, and the expression level of LC3B decreased after silencing PINK1. The levels of urea nitrogen and creatinine of mice with Nanometer sinomenine treatment were lower than those of control group. The ROS, fibrotic proteins CollagenI, α-SMA, Fibronectin were significantly lower than that of control group, and the expression level of mitochondrial autophagy protein was significantly increased. Renal tubule boundary destruction, atrophy and collagen deposition were significantly lower than those in the control group.
Conclusion
Mitochondria-targeted nano sinomenine had a strong mitochondrial targeting effect on renal tubules,significantly enhances mitochondrial autophagy,inhibits ROS, CollagenI,α-SM production,and against renal fibrosis. It provides a new idea for the treatment of renal fibrosis and the transformation of basic experimental results.
Funding
- Government Support – Non-U.S.