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PMID: 8787685 Published · ppublish English Journal Article 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.

Interferon-gamma-mediated activation of STAT1alpha regulates growth factor-induced mitogenesis.

The Journal of clinical investigation ·Vol. 98 ·No. 5 ·1996-09-01 ·Pages 1218-30

Marra F, Choudhury GG, Abboud HE

Abstract

Immunomodulatory cytokines and growth factors act in a complex network to regulate diverse biologic processes. Pre-treatment of two types of human vascular pericytes, liver fat-storing cells or glomerular mesangial cells, with IFN-gamma dramatically enhanced DNA synthesis in response to PDGF or EGF. IFN-gamma by itself had very little effect on DNA synthesis. At least 24-h exposure of the cells to IFN-gamma is required for enhancement of growth factor-induced mitogenesis. IFN-gamma pretreatment did not influence PDGF or EGF receptor autophosphorylation, activation of phospholipase Cgamma1, and phosphatidylinositol 3-kinase, or mitogen-activated protein kinase activity. However, IFN-gamma pretreatment markedly potentiated the DNA binding activity of STAT1alpha in response to PDGF or EGF. Incubation of cells with antisense oligonucleotides targeting STATlalpha mRNA resulted in inhibition of DNA synthesis induced by the combination of IFN-gamma and PDGF or EGF. These data indicate that interaction between IFN-gamma and growth factors at the level of STAT1alpha results in increased DNA synthesis, and establish a role for STAT1alpha in this important biologic function of growth factors.

MeSH Terms
Adipocytes/cytology Blood Vessels/cytology Cell Division/drug effects Cell Line DNA/biosynthesis Drug Interactions Epidermal Growth Factor/pharmacology Glomerular Mesangium/cytology Growth Substances/pharmacology Humans Interferon-Stimulated Gene Factor 3 Interferon-gamma/pharmacology Liver/cytology Mesoderm/cytology,drug effects Oligonucleotides, Antisense/pharmacology Platelet-Derived Growth Factor/pharmacology Signal Transduction/drug effects Transcription Factors/genetics,metabolism
Chemicals
Growth Substances Interferon-Stimulated Gene Factor 3 Oligonucleotides, Antisense Platelet-Derived Growth Factor Transcription Factors gamma interferon activation factor Epidermal Growth Factor Interferon-gamma DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Marra F
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7882, USA.
Choudhury G G
Abboud H E
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118905
Published
1996-09-01
Pages
1218-30
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507544
Subset
IM
Grants
NIDDK NIH HHS · DK-33665 · United States
NIDDK NIH HHS · DK-43988 · United States
External Links
PubMed source DOI: 10.1172/JCI118905 PMC Full Text View journal details
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