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Turkish Journal of Biology

Abstract

Background: Abdominal aortic aneurysm (AAA), a gradual segmental dilatation of the abdominal aorta, is associated with a high mortality rate. The pathophysiological molecular mechanisms underlying AAA remain unclear. In recent years, changes in miRNA levels have been reported to be involved in the development and treatment of AAA. This study aimed to investigate the potential targets and underlying mechanisms of miR-9-5p in attenuating AAA progression by modulating the inflammatory response.

Materials and methods: Biochemical kits were used to measure the levels of inflammatory factors, antioxidant enzyme activity, and serum oxidative stress in normal and AAA model mice. miR-9-5p overexpression was achieved by transfecting miR-9-5p mimics into CD4+ T cells and administering an miR-9-5p agomir to the mice. The effect of miR-9-5p overexpression was evaluated by detecting the expression level of miR-9-5p in CD4+ T cells through qRT‒PCR. The NF-κB/Nrf2 pathway levels were assessed using immunofluorescence, western blotting, and quantitative PCR. miR-9-5p expression was modulated by transfecting either miR-9-5p mimics or inhibitors, and the impact on CD4+IL-10+ T-cell differentiation was analyzed using flow cytometry.

Results: Compared with that in the control group, miR-9-5p expression in CD4+ T cells from the peripheral blood of AAA model mice was decreased by 28%. In vivo, miR-9-5p intervention reduced AAA formation in model mice and markedly decreased serum oxidative stress damage and inflammatory factor levels. Furthermore, miR-9-5p intervention significantly increased miR-9-5p levels in CD4+ T cells both in vitro and in vivo, increased the proportion of CD4+IL-10+ T cells, suppressed NF-κB expression, and upregulated Nrf2 and its downstream antioxidant genes. Conversely, these therapeutic effects were abolished when an miR-9-5p inhibitor was administered.

Conclusions: By controlling the interaction between the Nrf2 and NF-κB signaling pathways, miR-9-5p mediates the differentiation of CD4+IL-10+ T cells and alleviates the development of AAA.

Author ORCID Identifier

HONGFU LIU: 0009-0004-5913-991X

JINYI ZHANG: 0009-0000-4143-0603

LUBIN LI: 0000-0003-2677-5819

BENXIANG YU: 0009-0005-5446-8316

CHUNLEI ZHANG: 0009-0002-0210-3516

WENQIANG NIU: 0009-0004-9969-8054

YAWEN CHENG: 0009-0009-4178-8491

HENGYANG DONG: 0000-0001-6352-669X

YUKUN ZHANG: 0009-0005-2425-5491

XINLIN LUO: 0009-0004-4873-5601

YANLIAN XIONG: 0000-0001-5178-8932

YUEMING WANG: 0000-0003-1375-8737

DOI

10.55730/1300-0152.2754

Keywords

Abdominal aortic aneurysm, miR-9-5p, Nrf2, oxidative stress, CD4+ T cells

First Page

380

Last Page

391

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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