FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc.
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 2 (FGF2), 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 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) 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 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally 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.
Nakayama
Takayuki
T
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Mutsuga
Noriko
N
Tosato
Giovanna
G
D000818:Animals; D001854:Bone Marrow Cells; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006412:Hematopoietic Stem Cells; D051379:Mice; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism*
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1