Submitted June 9, 2006
Accepted October 3, 2006
FGF2 post-trancriptionally downregulates expression of SDF-1 in bone marrow stromal cells through FGFR1 IIIc
Takayuki Nakayama*, Noriko Mutsuga, and Giovanna Tosato
National Institute of Health
* Corresponding author; email: nakayamt{at}mail.nih.gov.
The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor (FGF) 2, a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 expression, FGF2 compromised stromal cell support of hematopoietic progenitor cells. RT-PCR analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFR) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 expression in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by post-trancriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.
