AI Article Synopsis
- - Efferocytosis is an important process where macrophages clear dying cells, helping to control inflammation and prevent further cell death, but its role in acute pancreatitis (AP) is not well understood.
- - The study found that injured pancreatic tissues from humans and mice showed increased levels of CD47, a molecule that signals cells not to be eaten, and identified its regulation by the transcription factor TRIM28 and the microRNA miR-133a.
- - Using gene editing and other techniques, the research demonstrated that CD47's role in efferocytosis is key to preventing pancreatic cell death in AP, suggesting that targeting the TRIM28-miR133a-CD47 pathway might be a promising treatment strategy. *
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11403229 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2024.06.005 | DOI Listing |
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