Regulatory Mechanisms Within Multicellular Signaling Networks in Liver Ischemia–Reperfusion Injury: A Systematic Review Focusing on Cell‐Type‐Specific Interactions

Abstract

Hepatic ischemia–reperfusion injury (HIRI) is a common and severe complication in various clinical scenarios, such as liver transplantation, hepatectomy, and liver trauma, significantly affecting patient prognosis and potentially leading to liver failure. The mechanism of HIRI is complex, involving dynamic interactions among multiple cell types in the liver, primarily comprising hepatocytes, Kupffer cells (KCs), hepatic stellate cells (HSCs), and hepatic sinusoidal endothelial cells (LSECs). Current studies indicate that these cells mediate the inflammatory response, oxidative stress, and cell death processes through signaling pathways, forming the core mechanism of liver tissue damage. However, the intercellular regulatory network has not been fully elucidated, limiting the development of effective therapeutic strategies. This article systematically reviews the mutual regulatory mechanisms of various liver cells during hepatic ischemia–reperfusion, focusing on intercellular signal communication and pathophysiological changes, and integrates recent advancements to evaluate their potential applications in disease prevention and treatment, aiming to provide theoretical support and novel therapeutic approaches for clinical interventions in HIRI.