Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.

Liver fibrosis, as a common pathological process in various chronic liver diseases, severely impacts patients' quality of life and prognosis. The core mechanisms driving its progression involve the activation of hepatic stellate cells (HSCs), sustained inflammatory responses, and cellular metabolic reprogramming. Within this process, hypoxia-inducible factor-1 (HIF-1), a key transcription factor enabling cellular adaptation to hypoxic environments, has been shown to play a significant role. Current research further demonstrates that HIF-1 participates in multiple molecular mechanisms of liver fibrosis by regulating HSC activation, promoting inflammation, and modulating metabolic pathways. However, the precise regulatory networks of HIF-1 in liver fibrosis and effective intervention strategies remain poorly understood.Therefore, this article systematically reviews the molecular regulatory network of HIF-1 in liver fibrosis, with a particular focus on its role in cell apoptosis and metabolic reprogramming. Furthermore, it summarizes recent advances in therapeutic strategies targeting HIF-1 and its related signaling pathways, including the development and application of HIF-1 inhibitors, natural products, and small-molecule drugs. In summary, by integrating the latest basic and clinical research findings, this review aims to provide theoretical support and identify future research directions for targeted therapy of liver fibrosis, thereby facilitating the clinical translation of relevant treatment approaches.