Hypoxia-inducible factor-1alpha in hepatic fibrosis: A promising therapeutic target

Hypoxia-inducible factor-1alpha (HIF-1α) is a regulated subunit of the hypoxia-inducible factor 1 (HIF1), which functions as a key transcription factor in response to hypoxic stress by regulating genes involved in maintaining oxygen homeostasis. In recent years, a growing body of studies showed that HIF-1α was significantly increased in hepatic fibrotic tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of HIF-1α expression inhibited the proliferation and activation of HSCs. In addition, HIF-1α-dependent genes and the extensive network of signaling cascades focus on HIF-1α have been reported to associate with the development of hepatic fibrosis, suggesting that HIF-1α might play a crucial role in hepatic fibrosis. However, the mechanisms by which HIF-1α regulates hepatic fibrosis are still undefined. In this review, we concentrate on multiple signaling pathways and genes related with HIF-1α which may be involved in the development of hepatic fibrosis, further discussing its potential as a novel therapeutic target for hepatic fibrosis.