MiR-33-Mediated Regulation of Autophagy and Inflammation in CIK Cells Through Atg5

被引：0

作者：

Yang, Lulu ^{[1
]}

Lin, Mengjun ^{[1
]}

Zhao, Weifang ^{[1
]}

Zhang, Yuru ^{[1
]}

Xu, Xinxin ^{[1
]}

Cao, Xianglin ^{[1
]}

Nie, Guoxing ^{[1
]}

Lu, Ronghua ^{[1
]}

机构：

[1] Henan Normal Univ, Coll Fisheries, Xinxiang, Peoples R China

来源：

JOURNAL OF FISH DISEASES | 2025年

关键词：

Atg5; Autophagy; CIK cells; Inflammation; MiR-33; MACROPHAGE AUTOPHAGY; IMMUNE-RESPONSE; MIR-33; MICRORNAS; MECHANISM; MICE;

D O I：

10.1111/jfd.14101

中图分类号：

S9 [水产、渔业];

学科分类号：

0908 ;

摘要：

MicroRNA-33 (miR-33) plays a critical role in the regulation of autophagy and inflammatory responses. In this study, C. idella kidney (CIK) cells were transfected with a miR-33 mimic or inhibitor and Atg5 was overexpressed or silenced to elucidate the regulatory mechanism of miR-33. Our findings revealed that the miR-33 mimic significantly decreased the expression of LC3B (a marker of autophagy activation), and the level of autophagy-related genes (Beclin-1, Atg5 and LC3-1) was also significantly downregulated (p < 0.05). Additionally, the miR-33 mimic promoted the secretion of proinflammatory factors, including TNF-alpha, IL-6, IL-12 and IL-1 beta (p < 0.05). In contrast, the miR-33 inhibitor significantly enhanced LC3B protein expression and increased the relative expression of Beclin-1 and Atg5 (p < 0.05). The secretion of proinflammatory factors (TNF-alpha, IL-6 and IL-12) was significantly reduced (p < 0.05). These results suggested that inhibition of miR-33 could induce the initiation of autophagy and attenuate the inflammatory response in CIK cells. Furthermore, we identified Atg5 as a direct target gene of miR-33. Overexpression of Atg5 significantly upregulated the levels of Beclin-1, Atg5, Atg4C and LC3-1, along with a reduction in the secretion of proinflammatory factors (TNF-alpha, IL-12 and IL-1 beta). Besides, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased (p < 0.05). Conversely, interference with Atg5 expression caused significant downregulation in the expression levels of Beclin-1, Atg5, Atg12, Atg4C and LC3-1, resulting in increased secretion of TNF-alpha, IL-12 and IL-1 beta and decreased activity of acid phosphatase (ACP) and SOD (p < 0.05). Taken together, these results suggested that inhibition of miR-33 expression could promote the initiation of autophagy and attenuate the inflammation in CIK cells through targeting Atg5. This study not only enhances the understanding of the mechanism by which miR-33 regulates autophagy and inflammation in fish but also provides a theoretical foundation and novel insights to improve disease management in the fish aquaculture industry.

引用

页数：9