Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo

Amifostine does not prevent activation of TGF beta 1 but induces smad 7 activation in megakaryocytes irradiated in vivo

Author Segreto, Helena Regina Comodo Autor UNIFESP Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Kimura, Edna Teruko Autor UNIFESP Google Scholar
Franco, Marcello Autor UNIFESP Google Scholar
Egami, Mizue Imoto Autor UNIFESP Google Scholar
Silva, Maria Regina Regis da Autor UNIFESP Google Scholar
Segreto, Roberto Araujo Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. in amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo. (C) 2002 Wiley-Liss, Inc.
Keywords bone marrow
gamma rays
TGF beta
smad cascade
Language English
Date 2002-11-01
Published in American Journal of Hematology. New York: Wiley-liss, v. 71, n. 3, p. 143-151, 2002.
ISSN 0361-8609 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 143-151
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000178973900001

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