Aberrant Smad2/3 Signaling

The TGF-β superfamily comprises multifunctional signaling proteins and key regulators of homeostasis and repair throughout the body.1 Dysfunction of members has been implicated in cancer and other pathological conditions. Ligands in this superfamily mediate their diverse effects by inducing distinct combinations of type I and II receptors and their downstream effectors—Smad proteins.1

Preclinical studies have shown that Smad2/3 signaling mediated by members of the TGF-β superfamily may have effects on erythroid precursors2-4 and is involved in regulating late-stage erythropoiesis.5-7 However, the specific roles of Smad2/3 signaling in red blood cell production have not been fully elucidated. A preclinical study showed that inhibition of Smad2/3 activation promoted terminal erythroid differentiation in a beta-thalassemia murine model.8

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Piek E, et al. FASEB J. 1999;13:2105-2124.
  2. Blank U, Karlsson S. Leukemia. 2011;25:1379-1388.
  3. Shiozaki M, et al. Proc Natl Acad Sci U S A. 1992;89:1553-1556.
  4. Shav-Tal Y, Zipori D. Stem Cells. 2002;20:493-500.
  5. Carrancio S, et al. Br J Haematol. 2014;165:870-882.
  6. Suragani RN, et al. Nat Med. 2014;20:408-414.
  7. Zermati Y, et al. Exp Hematol. 2000;28:885-894.
  8. Suragani RN, et al. Blood. 2014;123:3864-3872.