Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors.
Macrophage colony-stimulating factor (M-CSF) selectively promotes mononuclear phagocyte survival, proliferation, and differentiation. The production of this factor within the liver may be necessary to support the relatively long-term survival of circulating monocytes as they migrate into tissues and differentiate into macrophages. We studied the constitutive expression and the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on M-CSF mRNA levels and secretion of M-CSF in murine liver fat-storing cells (FSC), vascular pericytes likely involved in the development of liver fibrosis. By Northern analysis, using a murine M-CSF cDNA, FSC constitutively express two major transcripts of 4.4 and 2.2 kb, similar to those detected in mouse L cells, used as a control. Exposure to 10 ng/ml PDGF or bFGF increased M-CSF mRNA levels. Peak effects were observed at 3 and 6 h for PDGF and bFGF, respectively, returning to baseline levels by 12 h. Under basal conditions, detectable amounts of M-CSF, measured by radioimmunoassay, were found in cell supernatants conditioned for 8 and 24 h. PDGF and bFGF markedly stimulated the release of M-CSF as early as 8 h, an effect persisting for at least 24 h. These findings suggest that liver FSC release M-CSF upon stimulation by PDGF and bFGF and may contribute to the activation of resident or infiltrating cells in inflammatory liver diseases.
Pinzani
M
M
Istituto di Clinica Medica II, University of Florence, Italy.
Abboud
H E
HE
Gesualdo
L
L
Abboud
S L
SL
D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D013936:Thymidine