During hematopoiesis, expression of FLRG, a novel activin A ligand, is regulated by TGF-beta

Objective. The human gene FLRG, identified from a B-cell chronic lymphocyti c leukemia bearing a t(11;19) translocation, encodes a secreted glycoprotei n highly homologous with follistatin. Activin A is a TGF-beta family member involved in the regulation of growth and differentiation of various types of cells, such as those of the hematopoietic system. Its biological activit y is antagonized by binding with follistatin. We investigated the binding o f FLRG to activin A and the expression pattern of FLRG, follistatin, and ac tivin A during hematopoiesis. Materials and Methods. The binding of FLRG with activin A was investigated by immunoprecipitation and Far-Western blot analysis. Gene expression was a nalyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and Nor thern Blot in purified hematopoietic populations. Results. We demonstrate that FLRG, like follistatin, is able to bind to act ivin A. In bone marrow stromal cells, both mRNA and protein FLRG levels wer e found to be dramatically increased by TGF-beta. FLRG and activin A are ex pressed in the same cells, with a higher level of expression in the myeloid cells compared with the erythroid and megakaryocytic cells. FLRG and folli statin expression were different in the hematopoietic subpopulations tested . Moreover, we observed that FLRG and activin A expression was up-regulated during hematopoiesis. Conclusion. FLRG and activin A are expressed in the same hematopoietic cell and regulated by TGF-beta. Moreover, FLRG interacts,vith activin A, sugges ting that FLRG, like follistatin, participates in the diverse regulatory fu nctions of activin A, such as those in hematopoiesis. (C) 2001 Internationa l Society for Experimental Hematology. published by Elsevier Science Inc.