Figure 10. Schematic illustration of oxygen→ARSB→C4S→galectin-3→AP-1→HIF-1α signaling pathway.

Normoxic and hypoxic conditions lead to differences in signaling, attributable to reduced ARSB activity leading to increase in chondroitin-4-sulfation, reduced galectin-3 binding to the more highly sulfated C4S, increased nuclear translocalization of galectin-3, and increased transcriptional events in association with activation of AP-1, including increased expression of HIF-1α. [ARSB = arylsulfatase B; FGE = formylglycine (oxoalanine) generating enzyme; C4S = chondroitin-4-sulfate].