Abstract: PO2134
Increases in Renal CD81 and NCC Are Associated with Lipopolysaccharide-Induced Preeclampsia
Session Information
- Mechanisms of Kidney and Vascular Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Wang, Ping, enQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, Jiangsu, China
- Zhu, Gangyi, enQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, Jiangsu, China
- Jia, Yutao, enQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, Jiangsu, China
- Yu, Yanting, enQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, Jiangsu, China
- Wang, Xiaoyan, enQ Hospital of Nanjing Medical University, the Fourth Clinical Medical College, Nanjing, Jiangsu, China
Background
CD81, a member of the tetraspain superfamily, is an important component in the pathogenesis of pregnancy hypertension while the status of renal salt transport proteins plays an important role in blood pressure (BP) regulation.
Methods
In order to explore whether there is a connection between the two in the process of preeclampsia, we studied the interaction of CD81 and Na+-Cl- cotransporter (NCC) in vivo and in vitro.
Results
A rat model of pregnancy hypertension was built by injecting a small amount of lipopolysaccharide (LPS, 0.5μg/kg in 2ml saline) into the tail vein of pregnant rats on GD 5. On GD 18, BPs (SBP :99.9±1.4 vs 116.9±1.8，DBP :85.9±2.0 vs 94.4±1.8,mmHg, n=7/group) and urine protein (1185±35.0 vs 3550±158.0, μg/day, n=4/group) were higher in LPS -rats relative to vehicle-rats while renal protein abundance of CD81 (186.7±20, % of vehiclel, n=4/group, same as below) and NCC (278.0±53) was increased. The interaction of CD81 and NCC was found in the co-immunoparticipation complexes from rat kidney homogenates with the antibodies against CD81 or NCC. In order to further explore the relationship between renal CD81 and NCC, we treated mouse kidney distal tubule cells with LPS for 24h to construct an in vitro experimental model. The cell viability, detected by CCK-8, was not affected at all concentrations of LPS (0, 1, 10, 20, 30, μg/ml). The toxicity of LPS, detected by LDH release studies, was increased at concentrations of 20 (108.0 ± 3.4, n=6/group) and 30μg/ml (115.5±3.3) respectively but not altered at the lower concentrations. Relative to vehicle, LPS at concentration of 10ug / ml increased the protein abundance of CD81 (161.5 ± 23.22, n=6/group) and TNF-α (207.5 ± 27.67) but did not change the protein abundance of MCP-1. The protein abundance of NCC (193.5 ± 27.86) was increased remarkably while α1-NKA was also increased slightly (134.3 ± 4.51). The mRNA expression of CD81 mRNA was increased at LPS concentrations (μg/ml) of 1(154.9 ±11.13, % of vehicle, n=6/group), 10 (134,2±10.54)，20 (148.0±8.61),30 (139.3±20.9) respectively.
Conclusion
Our findings in vivo and in vitro suggest that LPS can cause an increase in protein abundance and mRNA expression of CD81 and up-regulate NCC in renal distal convoluted tubules, which may contribute to an increase in blood pressure in pregnancy rats.