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. 2018 Jun 11;94(6):248–258. doi: 10.2183/pjab.94.017

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© 2018 The Japan Academy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 5. — Model of Regnase-1-mediated regulation of iron uptake in the duodenum. Regnase-1 destabilizes PHD3 mRNA, thereby increasing the activity of HIF2α, a critical regulator of iron homeostasis in the duodenum. Accumulated HIF2α then induces the up-regulation of iron transporters and reductases (Dmt1, Ferroportin and Dcytb), leading to adequate iron uptake. Moreover, Regnase-1 itself is transcriptionally up-regulated via HIF2α under iron-deficient conditions. Therefore, the Regnase-1-PHD3-HIF2α axis forms a positive feedback loop for HIF2α amplification to regulate iron uptake in the duodenum.