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Elevated reactivity of Apelin inhibited renal fibrosis induced by chronic intermittent hypoxia
Yurong Wang1, Yan Wang1, Kai Xue1
1Key Laboratory of Applied Pharmacology in Universities of Shandong, Department of Pharmacology, School of Pharmacy, Weifang Medical University, Weifang, 261053, Shandong, China.
Background:
Apelin and its receptor angiotensin receptor - like 1 (APJ) are closely related to renal fibrosis, but their specific roles in renal fibrosis are still controversial. In this article, we discussed the role of Apelin/APJ system in renal fibrosis and its mechanism.
Methods:
Chronic intermittent hypoxia (CIH) rat model was established to induce the environment of renal fibrosis and a competitive antagonist of the APJ receptor ML221 was administered to CIH rats. The rats were divided into Control, CIH and ML221 groups. HE staining was used to detect the inflammatory injury and fibrosis of renal tissue. The expressions of renal fibrosis-related indicators transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and Human type I collagen (Col-Ⅰ) were detected by immunohistochemistry. The levels of oxidative stress indexes reactive oxygen species (ROS), Malondialdehyde (MDA), Superoxide Dismutase (SOD) and inflammation-related indexes Interleukin (IL) -6, tumor necrosis factor-α (TNF-α) and IL-1β were detected by ELISA. At the same time, the levels of Apelin-13 and AngiotensinII (AngⅡ) were also measured by ELISA. Finally, western blot was used to detect the expression of Apelin pathway and renal fibrosis-related proteins. In addition, at the cellular level, we divided the cells into Control, CIH, Apelin-13 and Apelin-13+ML-221 groups to further verify the specific mechanisms at the cellular level.
Results:
The expression of Apeline-13 and its related pathways was significantly increased after the induction of CIH in rats. However, the degree of renal fibrosis in ML221 group was further significantly increased after inhibiting the expression of Apelin. At the cellular level, CIH model cells treated with Apelin-13 significantly reduced cell proliferation, oxidative stress and inflammatory response, and decreased the expression of fibrosis-related proteins, which can be reversed by ML221 administration.
Conclusion:
The increased reactivity of Apelin may be one of the protective mechanisms against renal fibrosis induced by CIH.
Insights
The Apelin/APJ system plays a protective role in chronic intermittent hypoxia-induced renal fibrosis. Inhibiting Apelin exacerbates fibrosis, while Apelin-13 treatment shows protective effects against renal fibrosis.
Area of Science:
- Nephrology
- Cardiovascular Research
- Cell Biology
Background:
- The Apelin/APJ system's role in renal fibrosis is debated.
- Understanding its mechanism is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of the Apelin/APJ system in chronic intermittent hypoxia (CIH)-induced renal fibrosis.
- To elucidate the underlying mechanisms of Apelin's action in renal fibrosis.
Main Methods:
- A rat model of CIH was established and treated with ML221, an APJ receptor antagonist.
- Renal fibrosis markers (TGF-β, α-SMA, Col-Ⅰ), oxidative stress (ROS, MDA, SOD), and inflammation (IL-6, TNF-α, IL-1β) were assessed.
- Apelin-13 levels, Angiotensin II, and protein expressions were measured using ELISA and Western blot.
- Cellular studies further validated mechanisms using CIH model cells treated with Apelin-13 and ML221.
Main Results:
- CIH significantly increased Apelin-13 and related pathway expressions.
- Inhibition of Apelin by ML221 exacerbated renal fibrosis.
- Apelin-13 treatment in CIH model cells reduced proliferation, oxidative stress, and inflammation, decreasing fibrosis-related proteins.
Conclusions:
- Increased Apelin reactivity appears to be a protective mechanism against CIH-induced renal fibrosis.
- The Apelin/APJ system holds potential as a therapeutic target for renal fibrosis.
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