Affiliation:
1. Department of Immunology Zunyi Medical University Zunyi Guizhou China
2. Key Laboratory of Gene Detection and Treatment of Guizhou Province Zunyi Guizhou China
3. School of Medicine Guizhou University Guiyang Guizhou China
4. Department of Medical Physics Zunyi Medical University Zunyi Guizhou China
5. Kweichow Moutai Hospital Renhuai Guizhou China
Abstract
AbstractAging is intricately linked to immune system dysfunction. Recent studies have highlighted the biological function of microRNA‐7 (miR‐7) as a novel regulator of immune cell function and related diseases. However, the potential role of miR‐7 in aging remains unexplored. Here, we investigated the contribution of miR‐7 to d‐gal‐induced aging in mice, focusing on its regulation of senescent Kupffer cells. Our findings revealed that miR‐7 deficiency significantly ameliorated the aging process, characterized by enhanced CD4+ T‐cell activation. However, the adoptive transfer of miR‐7‐deficient CD4+T cells failed to improve the age‐related phenotype. Further analysis showed that miR‐7 deficiency significantly reduced IL‐1β production in liver tissue, and inhibiting IL‐1β in vivo slowed down the aging process in mice. Notably, IL‐1β is mainly produced by senescent Kupffer cells in the liver tissue of aging mice, and miR‐7 expression was significantly up‐regulated in these cells. Mechanistically, KLF4, a target of miR‐7, was down‐regulated in senescent Kupffer cells in aging mouse model. Furthermore, miR‐7 deficiency also modulated the NF‐κB activation and IL‐1β production in senescent Kupffer cells through KLF4. In conclusion, our findings unveil the role of miR‐7 in d‐gal‐induced aging in mice, highlighting its regulation of KLF4/NF‐κB/IL‐1β pathways in senescent Kupffer cells. This research may enhance our understanding of miRNA‐based aging immune cells and offer new avenues for new intervention strategies in aging process.
Funder
National Natural Science Foundation of China
Cited by
3 articles.
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