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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Bone. 2020 Jun 23;138:115495. doi: 10.1016/j.bone.2020.115495

Figure 4. Crosstalk between inflammation and the BMP-SMAD pathway in hepcidin regulation.

Figure 4.

During inflammation, interleukin (IL)-6 binds to its receptor to activate Janus Kinases (JAK)2, which induces the dimerization and phosphorylation of the signal transducer and activator of transcription (STAT)3. Phosphorylated STAT3 translocates to the nucleus and binds to a STAT3 response element (SRE) to upregulate hepcidin transcription. An intact BMP-SMAD1/5/8 signaling pathway is necessary for optimal hepcidin induction by inflammation by controlling basal hepcidin expression. Activin B is also generated during inflammation. In hepatocyte cell cultures, Activin B can utilize Activin type II receptors (ACVR2A and ACVR2B) and BMP type I receptors (ALK3 and ALK2) to activate SMAD1/5/8 signaling and induce hepcidin production, although a study in Inhbb−/− knockout mice (which lack Activin B) did not support a role for Activin B in hepcidin regulation by inflammation in vivo.