To investigate the role of Z-DNA binding protein 1 (ZBP1) in macrophage pyroptosis and polarization in ulcerative colitis (UC), highlighting its significance as a therapeutic target, and to evaluate the therapeutic potential of Emapunil.
Key Findings:
ZBP1 was significantly upregulated in colorectal macrophages from UC patients.
Overexpression of ZBP1 induced macrophage pyroptosis and M1 polarization, activating the NF-κB pathway and impairing intestinal barrier integrity.
ZBP1 knockdown reversed the effects of overexpression.
Emapunil suppressed macrophage pyroptosis and inflammatory polarization by downregulating ZBP1, alleviating DSS-induced colonic injury and preserving intestinal barrier function in mice, potentially through targeting TSPO.
Interpretation:
ZBP1 aggravates intestinal inflammation and barrier damage by driving macrophage pyroptosis and pro-inflammatory polarization, indicating its role as a key regulator in UC and a promising therapeutic target.
Limitations:
Potential limitations include the specificity of Emapunil's action on ZBP1 and the need for further validation in human studies.
Conclusion:
Emapunil exerts anti-UC effects through downregulation of ZBP1, providing a novel mechanism and potential therapeutic strategy for managing ulcerative colitis.
