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TGFβ2 upregulates transcription of hepcidin by the canonical, Smad-dependent pathway. Autocrine and paracrine activity of hepcidin downregulates Fpn, resulting in intracellular accumulation of iron, compensatory upregulation of ferritin, and increase in ROS, which upregulates TGFβ2. Heparin, a hepcidin antagonist, and antioxidants inhibit upregulation of TGFβ2 by decreasing ROS, disrupting the cycle (Ashok et al., 2020a).
