Expression of FLRG, a novel activin A ligand, is regulated by TGF-beta and during hematopoiesis [corrected]

The human gene FLRG, identified from a B-cell chronic lymphocytic leukemia bearing a t(11;19) translocation, encodes a secreted glycoprotein 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 activity is antagonized by binding with follistatin. We investigated the binding of FLRG to activin A and the expression pattern of FLRG, follistatin, and activin A during hematopoiesis.

The binding of FLRG with activin A was investigated by immunoprecipitation and Far-Western blot analysis. Gene expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern Blot in purified hematopoietic populations.

We demonstrate that FLRG, like follistatin, is able to bind to activin A. In bone marrow stromal cells, both mRNA and protein FLRG levels were found to be dramatically increased by TGF-beta. FLRG and activin A are expressed in the same cells, with a higher level of expression in the myeloid cells compared with the erythroid and megakaryocytic cells. FLRG and follistatin expression were different in the hematopoietic subpopulations tested. Moreover, we observed that FLRG and activin A expression was up-regulated during hematopoiesis.

FLRG and activin A are expressed in the same hematopoietic cells and regulated by TGF-beta. Moreover, FLRG interacts with activin A, suggesting that FLRG, like follistatin, participates in the diverse regulatory functions of activin A, such as those in hematopoiesis.