Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors

Am J Physiol. 1992 Apr;262(4 Pt 1):C876-81. doi: 10.1152/ajpcell.1992.262.4.C876.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • DNA / biosynthesis
  • Epidermal Growth Factor / physiology*
  • Fibroblast Growth Factor 2 / physiology*
  • Immunohistochemistry
  • Lipid Metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Liver / physiology
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Platelet-Derived Growth Factor / physiology*
  • RNA, Messenger / metabolism
  • Thymidine / metabolism
  • Transcription, Genetic

Substances

  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Macrophage Colony-Stimulating Factor
  • DNA
  • Thymidine