Low doses of EPO activate MAP kinases but not JAK2-STAT5 in rat vascular smooth muscle cells

Previous reports have shown a direct effect of erythropoietin (Epo) on vasc ular smooth muscle cells (VSMCs). Our aim was to assess expression of the E po receptor (EpoR) on VSMCs and to study the activation of two major signal ing cascades activated by Epo, namely JAK2/STAT5 and MAPK pathways. All exp eriments were performed in parallel using the Epo-responsive UT7 cell line. From semiquantitative RT-PCR experiments, VSMCs were estimated to express similar to 30-fold less EpoR mRNA than UT7 cells. Epo-induced phosphorylati on of proteins involved in the EpoR/JAK2/STAT5 cascade could not be detecte d in VSMCs, even using pharmacological doses of Epo (250 IU/ml). In contras t, a strong activation of MAP kinase pathway was detected with as low as 10 IU/ml Epo. We suggest that MAPK activation reflects a physiologically rele vant effect of Epo on VSMCs that may be correlated to cell proliferation. ( C) zool Academic Press.