Hypoxia-inducible factor-1: A potential pharmacological target to manage psoriasis

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor and is composed of HIF-1α and HIF-1β subunits. An increase in the levels of HIF-1α in the psoriatic lesions and the serum of psoriatic patients has been reported. An increase in the HIF-1α in the epithelial keratinocytes may contribute in promoting angiogenesis and skin inflammation. Accordingly, the drug therapy directed to control HIF-1α levels may effectively manage the disease. An increase in HIF-1α may participate in the pathogenesis of psoriasis in association with IL-6, vascular endothelial growth factor (VEGF), microRNA-150, microRNA-270, reactive oxygen species, bone morphogenetic protein 6 (BMP6), triggering receptor expressed on myeloid cells 1 (TREM-1) and phosphoinositide 3-kinases (PI3K)/Akt pathway. An increase in the levels of IL-6, free radicals, and reduction in miR-150 may increase the expression of HIF-1α, which may act to induce angiogenesis via VEGF-ERK2 signaling pathway. An increase in HIF-1α may attenuate the expression of BMP6 to inhibit the terminal differentiation and increase the proliferation of keratinocytes. Moreover, HIF-1α may increase the expression of miR-210 to decrease the levels of STAT-6 and LYN, which in turn is manifested in the form of excessive activation of immune system. An increase in keratinocyte proliferation, excessive angiogenesis along with abnormal activation of the immune system play a key role in the pathogenesis of psoriasis. The present review discusses the evidence showing the crucial role of HIF-1α in psoriasis along with interrelationship with other mediators/signaling pathways that may contribute to the development of psoriasis.