Smad2/3

The TGF-β superfamily comprises multifunctional signaling proteins and key regulators of homeostasis and repair throughout the body.1 Dysfunction of TGF-β superfamily 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 Defective late-stage erythropoiesis results in impaired red blood cell maturation, leading to anemia and contributing to iron overload.8,9 However, the specific roles of Smad2/3 signaling in red blood cell production have not been fully elucidated. In a mouse model of β-thalassemia, inhibition of abnormally elevated Smad2/3 signaling improved hematology parameters associated with ineffective erythropoiesis.10

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References

  1. Piek E, et al. FASEB J. 1999;13:2105-2124. PMID: 10593858
  2. Blank U, Karlsson S. Leukemia. 2011;25:1379-1388. PMID: 21566654
  3. Shiozaki M, et al. Proc Natl Acad Sci U S A. 1992;89:1553-1556. PMID: 1542647
  4. Shav-Tal Y, Zipori D. Stem Cells. 2002;20:493-500. PMID: 12456957
  5. Carrancio S, et al. Br J Haematol. 2014;165:870-882. PMID: 24635723
  6. Suragani RN, et al. Nat Med. 2014;20:408-414. PMID: 24658078
  7. Zermati Y, et al. Exp Hematol. 2000;28:885-894. PMID: 10989189
  8. Attie KM, et al. Am J Hematol. 2014;89:766-770. PMID: 24715706
  9. Suragani RN, et al. Nat Med. 2014;20:408-414. PMID: 24658078
  10. Suragani RN, et al. Blood. 2014;123:3864-3872. PMID: 24795345