PROM2 exacerbates CCl4-Induced liver fibrosis via NLRP3 inflammasome activation and hepatocyte pyroptosis.

BACKGROUND

Liver fibrosis is a progressive disorder resulting from chronic liver injury, and its molecular mechanism remains incompletely elucidated.

METHODS

The role of PROM2 was assessed by integrating transcriptomic datasets with in vivo liver fibrosis models. Functional analyses were performed using PROM2 knockdown or overexpression strategies, along with NLRP3 knockout models, to investigate its mechanistic involvement in epithelial-mesenchymal transition (EMT) and inflammasome activation.

RESULTS

Transcriptomic analysis revealed that PROM2 expression was significantly upregulated in fibrotic livers and positively correlated with fibrosis- and EMT-related gene signatures. PROM2 knockdown significantly attenuated hepatic inflammation, inhibited EMT, and reduced fibrotic remodeling. In contrast, PROM2 overexpression aggravated these pathological features. Notably, in NLRP3-deficient mice, PROM2 overexpression failed to induce inflammation, EMT, or fibrosis, indicating that the pro-fibrotic effects of PROM2 are mediated through NLRP3 signaling.

CONCLUSION

PROM2 contributes to liver fibrosis by promoting EMT and activating NLRP3-dependent inflammatory pathways, suggesting it as a potential therapeutic target for liver fibrosis.