Research Article Intronic MicroRNA MiR-483-3p Modulates Oxidative Stress-induced Macrophage Apoptosis by Targeting MED1
by Xianlun Yin1#,Wenwen Teng2#, Xiaowei Wang1, Jing Gao1, Junjie Ma3*, Zhe Wang4*, Xiaoming Zhou5*
1State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, Qilu Hospital of Shandong University, China.
2Shandong Provincial Hospital, Affiliated to Shandong First Medical University, China
3Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, China
4Division of Geriatrics, Shandong Provincial Hospital affiliated to Shandong First Medical University, China
5Department of Research, Shandong Provincial Hospital Affiliated to Shandong First Medical University, China
# Equally contributed to this work
*Corresponding author: Xiaoming Zhou, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China. Zhe Wang, Division of Geriatrics, Shandong Provincial Hospital affiliated to Shandong First Medical University, China. Junjie Ma, Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, China.
Received Date: 26 September 2025
Accepted Date: 08 October 2025
Published Date: 23 October 2025
Citation: Yin X, Teng W, Wang X, Gao J, Ma J, et al. (2025) Intronic MicroRNA MiR-483-3p Modulates Oxidative Stress-induced Macrophage Apoptosis by Targeting MED1. J Med Biomed Discoveries 7: 143. https://doi.org/10.29011/2688-8718.100143
Abstract
Background: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. Oxidative stress, macrophage apoptosis, and miRNAs play important roles in its pathogenesis. This study investigated the role of miR-483-3p and its host gene IGF2 in oxidative stress-induced macrophage apoptosis during AAA progression, as well as the regulatory effects of γ-glutamylcysteine (γ-GC). Methods: AAA mouse models were established using Angiotensin II (Ang II) infusion. Macrophage apoptosis was quantified via co-localization of CD68 and TUNEL staining. RNA FISH, qPCR, and Western blot were employed to assess miR-483-3p, IGF2, MED1, p53, and p21 expression. The binding relationship between miR-483-3p and MED1 was verified via dual-luciferase assay. Flow cytometry analyzed the effects of H₂O₂ and γ-GC on macrophage apoptosis. Results: Macrophage apoptosis, intronic miR-483-3p and its host gene IGF2 expression in aneurysm tissue of AAA mice were significant increases, accompanied by a pronounced downregulation of γ-glutamylcysteine (γ-GC) synthetase. Although IGF2 markedly enhanced the pro-apoptotic effect of miR-483-3p, IGF2 alone had no significant effect on H₂O₂-induced macrophage apoptosis. Enrichment analysis revealed that miR-483-3p was involved in apoptosis process. MED1 was the target gene of miR-483-3p and inhibited the expression of pro-apoptotic genes p53 and p21. Furthermore, the pro-apoptotic effects of H₂O₂ and miR-483-3p on macrophages were significantly attenuated by γ-GC. Conclusion: In summary, we found that miR-483-3p promoted oxidative stress-induced macrophage apoptosis via MED1-p53/p21 axis with the collaboration of its host gene IGF2, which were significantly ameliorated by γ-GC.
Keywords: Abdominal aortic aneurysm; macrophage; miR-4833p; MED1; oxidative stress
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