1 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, UOC General Medicine, Milan, Italy.
2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
‡ The authors equally contributed to this work.
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β-thalassemia is a hereditary disorder caused by defective production of β-globin chains of hemoglobin (Hb) that leads to an increased α/β globins ratio with subsequent free α-globins.
Alpha globin excess causes oxidative stress, red blood cells membrane
damage, premature death of late-stage erythroid precursors, resulting
in ineffective erythropoiesis.
Activins and Activin Receptors
|Figure 1. TGF-β pathway and activin receptors ligand traps. A) Canonical signaling trough Smad2/3 activation.
Ligand binding induces dimerization of type II receptors and to
oligomerization with type I receptors; the activated multimers activate
Smad2/3s by phosphorylating them and triggering the formation of the
complex with Smad4. pSmad2/3-Smad4 complex translocates to the nucleus
regulating specific gene expression. Dimeric ligands and receptors
appear as monomers only to simplify the picture.
TGF-β and TGF-β Receptors
Activin Receptor II Ligand Traps
|Figure 1. TGF-β pathway and activin receptors ligand traps. B) Signaling inhibited by Activin receptors ligand traps.
Activin receptors ligand trap sequestrate the ligand, inhibiting the
pSmad2/3-Smad4 complex formation and favouring the interaction with
the nucleus, this complex should exert its action by inducing a
different transcriptional response. The specific ligand targeted has
not been identified yet. Dimeric ligands and receptors appear as
monomers only to simplify the picture.