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. 2024 Sep 4;32(9):3025-3041.
doi: 10.1016/j.ymthe.2024.06.005. Epub 2024 Jun 12.

The TRIM28/miR133a/CD47 axis acts as a potential therapeutic target in pancreatic necrosis by impairing efferocytosis

Qingtian Zhu  1 , Chenchen Yuan  1 , Dan Wang  2 , Bo Tu  3 , Weiwei Chen  4 , Xiaowu Dong  1 , Keyan Wu  1 , Lide Tao  1 , Yanbing Ding  1 , Weiming Xiao  1 , Lianghao Hu  5 , Weijuan Gong  6 , Zhaoshen Li  7 , Guotao Lu  8
Affiliations

The TRIM28/miR133a/CD47 axis acts as a potential therapeutic target in pancreatic necrosis by impairing efferocytosis

Qingtian Zhu et al. Mol Ther. .

Abstract

Efferocytosis, the clearance of apoptotic cells by macrophages, plays a crucial role in inflammatory responses and effectively prevents secondary necrosis. However, the mechanisms underlying efferocytosis in acute pancreatitis (AP) remain unclear. In this study, we demonstrated the presence of efferocytosis in injured human and mouse pancreatic tissues. We also observed significant upregulation of CD47, an efferocytosis-related the "do not eat me" molecule in injured acinar cells. Subsequently, we used CRISPR-Cas9 gene editing, anti-adeno-associated virus (AAV) gene modification, and anti-CD47 antibody to investigate the potential therapeutic role of AP. CD47 expression was negatively regulated by upstream miR133a, which is controlled by the transcription factor TRIM28. To further investigate the regulation of efferocytosis and reduction of pancreatic necrosis in AP, we used miR-133a-agomir and pancreas-specific AAV-shTRIM28 to modulate CD47 expression. Our findings confirmed that CD47-mediated efferocytosis is critical for preventing pancreatic necrosis and suggest that targeting the TRIM28-miR133a-CD47 axis is clinically relevant for the treatment of AP.

Keywords: acute pancreatitis; apoptotic cell clearance; clinical translation; immune microenvironment.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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