Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury.
Pyroptosis is linked to the development of acute lung injury (ALI), and circular RNAs (circRNAs) play a role in ALI-related inflammation. However, the mechanisms by which circRNAs contribute to macrophage pyroptosis in ALI remain unclear. This study constructed an in vitro ALI model by inducing THP-...
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0314936 |
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| author | Sida Chen Ling Wen Yumei Wu Shan Xiao Yuting Lai Jintao Ou Yan Shen |
| author_facet | Sida Chen Ling Wen Yumei Wu Shan Xiao Yuting Lai Jintao Ou Yan Shen |
| author_sort | Sida Chen |
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| description | Pyroptosis is linked to the development of acute lung injury (ALI), and circular RNAs (circRNAs) play a role in ALI-related inflammation. However, the mechanisms by which circRNAs contribute to macrophage pyroptosis in ALI remain unclear. This study constructed an in vitro ALI model by inducing THP-1 cells with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). The expression and potential mechanism of circ-CARD8 in macrophage pyroptosis were then investigated. The interaction between circ-CARD8, hsa-miR-580-3p, and caspase recruitment domain family member 8 (CARD8) was confirmed through luciferase reporter assays and RNA-binding protein immunoprecipitation. Our data showed that circ-CARD8 was expressed at low levels. Meanwhile, the pyroptotic proteins caspase-1 and GSDMD, along with the secretion of chemokine (C-C motif) ligand 18 and interleukin 1 beta, were upregulated in the ALI cell model. Overexpression of circ-CARD8 reversed macrophage pyroptosis, whereas inhibition of circ-CARD8 promoted it. Furthermore, the expression of miR-580-3p, a downstream microRNA that binds to circ-CARD8, was reduced upon circ-CARD8 overexpression and increased following its inhibition. Additionally, overexpression of miR-580-3p suppressed the expression of CARD8, a downstream target of miR-580-3p, thereby promoting macrophage pyroptosis. The inhibition of miR-580-3p reversed the effect of circ-CARD8 silencing on macrophage pyroptosis and CARD8 expression. Therefore, our study confirms that the low expression of circ-CARD8 reduces the sponge adsorption of miR-580-3p, increasing its expression, which in turn targets and inhibits CARD8, ultimately promoting macrophage pyroptosis induced by LPS in THP-1 cells. |
| format | Article |
| id | doaj-art-67ec3a22ec304adc892996afaa81ede7 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-67ec3a22ec304adc892996afaa81ede72025-01-08T05:32:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011912e031493610.1371/journal.pone.0314936Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury.Sida ChenLing WenYumei WuShan XiaoYuting LaiJintao OuYan ShenPyroptosis is linked to the development of acute lung injury (ALI), and circular RNAs (circRNAs) play a role in ALI-related inflammation. However, the mechanisms by which circRNAs contribute to macrophage pyroptosis in ALI remain unclear. This study constructed an in vitro ALI model by inducing THP-1 cells with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). The expression and potential mechanism of circ-CARD8 in macrophage pyroptosis were then investigated. The interaction between circ-CARD8, hsa-miR-580-3p, and caspase recruitment domain family member 8 (CARD8) was confirmed through luciferase reporter assays and RNA-binding protein immunoprecipitation. Our data showed that circ-CARD8 was expressed at low levels. Meanwhile, the pyroptotic proteins caspase-1 and GSDMD, along with the secretion of chemokine (C-C motif) ligand 18 and interleukin 1 beta, were upregulated in the ALI cell model. Overexpression of circ-CARD8 reversed macrophage pyroptosis, whereas inhibition of circ-CARD8 promoted it. Furthermore, the expression of miR-580-3p, a downstream microRNA that binds to circ-CARD8, was reduced upon circ-CARD8 overexpression and increased following its inhibition. Additionally, overexpression of miR-580-3p suppressed the expression of CARD8, a downstream target of miR-580-3p, thereby promoting macrophage pyroptosis. The inhibition of miR-580-3p reversed the effect of circ-CARD8 silencing on macrophage pyroptosis and CARD8 expression. Therefore, our study confirms that the low expression of circ-CARD8 reduces the sponge adsorption of miR-580-3p, increasing its expression, which in turn targets and inhibits CARD8, ultimately promoting macrophage pyroptosis induced by LPS in THP-1 cells.https://doi.org/10.1371/journal.pone.0314936 |
| spellingShingle | Sida Chen Ling Wen Yumei Wu Shan Xiao Yuting Lai Jintao Ou Yan Shen Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. PLoS ONE |
| title | Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. |
| title_full | Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. |
| title_fullStr | Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. |
| title_full_unstemmed | Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. |
| title_short | Circular RNA circ-CARD8 regulates alveolar macrophage pyroptosis through the miR-580-3p/CARD8 pathway in acute lung injury. |
| title_sort | circular rna circ card8 regulates alveolar macrophage pyroptosis through the mir 580 3p card8 pathway in acute lung injury |
| url | https://doi.org/10.1371/journal.pone.0314936 |
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