Abstract: SA-PO988
Knockdown of TMEM30A Resulted in Reduced Uric Acid Absorption
Session Information
- CKD: Pathobiology - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Chen, Pei Si, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
- Li, Guisen, Sichuan Academy of Medical Sciences and Sichuan People's Hospital, Chengdu, Sichuan, China
Background
Uric acid is the end product of purine metabolism in human body, and the main organ of its excretion is the kidney, accounting for about 70% of the daily excretion of uric acid. The reabsorption and secretion of uric acid in renal tubules are mainly completed by different transporters, among which uric acid anion transporter 1 is considered to be an important uric acid reabsorption transporter, accounting for more than 90% of the reabsorption. URAT1 is mainly expressed at the brush border of renal tubular epithelial cells and transports uric acid from the lumen to the renal tubular epithelial cells. P4-ATPase works together with β subunit TMEM30A to mediate the asymmetric distribution of aminoacyl phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), promote the fusion of plasma membrane and internal vesicles, and facilitate vesicular protein transport. We observed decreased TMEM30A expression in the renal tubules of DKD and IgA patients, suggesting a potential role for TMEM30A in renal tubular cells.
Methods
To study the role of Tmem30a in renal tubules, we constructed a TMEM30A knockdown cell model by transfecting renal tubular epithelial cells with TMEM30A siRNA. Subsequently, the expressions of TMEM30A, URAT1 and related proteins were detected by immunohistochemical staining, qPCR and Western blotting. At the same time, uric acid with different concentrations of 0, 0.1, 0.5 and 1.0 mmol/L was added, and its absorption was detected after 24, 48 and 72 h of treatment, respectively.
Results
The mRNA and protein expressions of URAT1 and vesicle transporter Rab6 were significantly decreased after TMEM30A knockdown, and the absorption of uric acid was significantly reduced.
Conclusion
Knockdown of TMEM30A in TCMK-1 cells reduces the synthesis of vesicular transporters, resulting in decreased transport and expression of URAT1, which in turn reduces the absorption of uric acid. Our data suggest that TMEM30A plays a crucial role in renal tubules.