Induction of erythroid proliferation and differentiation by a trophoblast-specific cytokine involves activation of the JAK/STAT pathway

Abstract

Pregnancy is characterized by increased erythropoiesis within maternal and fetal compartments. The placenta has been shown to produce factors that stimulate erythropoiesis but convincing evidence for placental production of erythropoietin (EPO) is still lacking. Prolactin-like protein E (PLP-E) was recently found to stimulate expression of the adult beta major globin gene in mouse erythroleukemia cells. Here we demonstrate that PLP-E transiently expressed in COS-7 cells stimulates proliferation and erythroid differentiation of murine and human erythroid progenitor cell lines. Electrophoretic mobility shift assays were used to show the activation of STAT5 by PLP-E in the human erythroid cell line TF1. Furthermore, we compared the effects of PLP-E on murine myeloid FDCP1 cells which do not express EPO receptors (EPORs) with effects on cells genetically engineered to express functional EPORs. We provide evidence that PLP-E-dependent proliferation and STAT5 activation is independent of the expression of the EPOR. Taken together, these data suggest that PLP-E acts on specific receptors of erythroid-committed murine and human cells by the activation of intracellular signaling pathways promoting cell growth and differentiation.

Migratory trophoblast cells express a newly identified member of the prolactin gene family

“…The temporal-and spatial-specific patterns of hormone production probably have an effect on hormone delivery and the biology of pregnancy. Members of the PRL family target and influence a wide range of maternal targets, including the reproductive tract, liver and other classic PRL targets (Goffin et al 2002), hematopoietic and immune systems (Lin & Linzer 1999, Müller et al1999, Bittorf et al 2000, Wang et al 2000, Ain et al 2002, Yu-Lee 2002 and vasculature (Jackson et al 1994, Corbacho et al 2002. Some members act via classical mechanisms involving the PRL receptor-signaling pathway, whereas others influence their targets via mechanisms that are at present not well understood.…”

Enhanced Recovery from Thrombocytopenia and Neutropenia in Mice Constitutively Expressing a Placental Hematopoietic Cytokine

“…This hormone has been found to stimulate proliferation and differentiation of erythroid cell lines (3). In experiments using myeloid progenitors from human bone marrow, mouse PLP-E was shown to act synergistically with thrombopoietin to enhance growth of CFU-MK, burst-forming unit erythroid (BFU-E) progenitors, and the common myeloid progenitor, CFU-granulocyte/ erythroid/macrophage/megakaryocyte (CFU-GEMM) (4).…”

Adaptive Evolution of the First Extra Exon in the Murid Rodent Prolactin Gene Family

“…Furthermore, functional shifts also exist among those members with extra exons. For example, the DPRP gene in the mouse seems to influence the ability of CHO cells to form tumors , and PLP-E and PLP-F regulate hematopoiesis (Lin and Linzer, 1999;Bittorf et al, 2000;Bhattacharyya et al, 2002). Additionally, proliferin and proliferin-related protein contain 5 and 6 exons, respectively, but they contribute to the process of angiogenesis in mouse as positive and negative regulators (Jackson et al, 1994).…”