Abstract | BACKGROUND: 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.
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Authors | Yurong Wang, Yan Wang, Kai Xue, Feng Gao, Chengde Li, Hui Fang |
Journal | Archives of biochemistry and biophysics
(Arch Biochem Biophys)
Vol. 711
Pg. 109021
(10 30 2021)
ISSN: 1096-0384 [Electronic] United States |
PMID | 34464591
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021. Published by Elsevier Inc. |
Chemical References |
- 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate
- Apelin
- Apelin Receptors
- Apln protein, rat
- Aplnr protein, rat
- Intercellular Signaling Peptides and Proteins
- Nitrobenzoates
- Pyrans
- apelin-13 peptide
- Angiotensin II
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Topics |
- Angiotensin II
(metabolism)
- Animals
- Apelin
(metabolism)
- Apelin Receptors
(antagonists & inhibitors)
- Cell Line
- Fibrosis
(etiology, metabolism, pathology)
- Humans
- Hypoxia
(complications)
- Inflammation
(etiology, metabolism)
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Kidney
(drug effects, pathology)
- Kidney Diseases
(etiology, metabolism, pathology)
- Male
- Nitrobenzoates
(pharmacology)
- Oxidative Stress
(drug effects)
- Pyrans
(pharmacology)
- Rats, Wistar
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