Abstract: TH-PO0256
Interplay Between Na/K-ATPase/Src/ROS Signaling and IL-6/Stat3 Pathway in Obesity-Induced Salt-Sensitive Hypertension
Session Information
- Hypertension and CVD: Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Cai, Jiahui, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Zhao, Shasha, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Sun, Feifei, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Pan, Qiaoyun, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Sun, Yunbo, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Wang, Danshu, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Wang, Shuo, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
- Liu, Weiping, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China
- Tan, Qiang, Peking University Third Hospital of Qinhuangdao, Qinhuangdao, China
- Pierre, Sandrine V., Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, West Virginia, United States
- Yan, Yanling, Key Labs Nanobiotech & Applied Chemistry, Department of Biotechnology & Engineering, College of Environmental & Chemical Engineering, Yanshan University, Qinhuangdao, China
Group or Team Name
- S&T Program of Hebei and Hebei Provincial Department of Human Resources and Social Security.
Background
We were the first to identify a novel role of Na/K-ATPase as a receptor in reactive oxygen species (ROS) signaling (Yan et al, JBC, 2013) and its involvement in obesity-induced salt-sensitive hypertension (ssHTN) (Yan et al, IJMS, 2019). The mechanisms responsible for ssHTN are incompletely understood and have been extended to inflammation. Interleukin-6 (IL-6), as a key inflammatory cytokine, promotes ssHTN. However, the impact of IL-6 on renal Na handling via Na/K-ATPase signaling-mediated has yet to be reported. This study investigates the interactions between oxidative stress and inflammation regarding ssHTN.
Methods
Two animal models of obesity were utilized to investigate the Na/K-ATPase/Src/ROS Signaling and IL-6/Stat3 Pathway. Diet-induced obese (DIO) C57BL/6J mice were used to examine the effects of Co(III) Protoporphyrin IX chloride (CoPP, an inducer of heme oxygenase, HO-1) on these signaling pathways, renal sodium handling and blood pressure regulation. Additionally, human and pig renal proximal tubular HK-2 and LLC-PK1 cells were employed for mechanistic analysis.
Results
Our findings revealed that IL-6/Stat3 signaling was activated in the renal cortex tissues of DIO C57BL/6J mice and leptin receptor-deficient obese Zucker rats (Figure 1). In DIO mice, CoPP inhibited the Na/K-ATPase signaling-mediated ROS generation, which impaired renal sodium excretion. This supports our previous findings that ROS is necessary for Na/K-ATPase/Src signaling-mediated natriuresis. Notably, CoPP shifted the renal function curve to the left, indicating reduced blood pressure, likely due to the inhibition of the IL-6/Stat3 signaling pathway (Figure 2).
Conclusion
IL-6/Stat3 signaling significantly contributes to obesity-induced ssHTN, with Na/K-ATPase being essential in this process. Targeting Na/K-ATPase/Src/ROS signaling and proinflammatory IL-6/Stat3 pathway could be a promising therapeutic strategy for treating ssHTN.
Funding
- NIDDK Support