Bromodomain protein 4 inhibitor JQ-1 alleviates hepatic ischemia-reperfusion injury by blocking the NLRP3/caspase-1 pathway
Year: 2025
Type: article
Abstract: BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major challenge in liver surgery and transplantation.Bromodomain protein 4 (BRD4) has emerged as a promising target due to its role in oxidative stress and inflammation.JQ-1, a specific BRD4 inhibitor, has shown protective effects on organs suffering I/R injury.This study aims to investigate the expression of BRD4 in liver tissues after I/R injury and to explore its role in this process using JQ-1 both in vivo and in vitro.METHODS: Our study established a mouse model of hepatic I/R injury and investigated the protective effect of JQ-1.We compared the histological features, BRD4 expression, and liver enzyme levels between JQ-1-treated and untreated groups.Additionally, the antioxidant properties of JQ-1 were analyzed in RAW 264.7 cells by evaluating cytokine expression, NLRP3 inflammasome activity, and reactive oxygen species production. RESULTS:Our results revealed that BRD4 was abundantly expressed in liver tissues after hepatic I/R injury, while JQ-1 treatment had antioxidant and hepatoprotective effects.JQ-1 also suppressed pro-inflammatory cytokine release in vitro.Furthermore, we clarified the mechanism by which JQ-1 enhances liver recovery through Kupffer cells by blocking the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)/caspase-1 pathway.CONCLUSION: JQ-1 has potential as a pre-clinical emergency therapy for hepatic I/R injury.Its ability to inhibit BRD4 and modulate the inflammatory response in Kupffer cells offers a promising avenue for future clinical intervention.
Authors: Li Wang, Weihua Gong
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4411679638