Synergistic effect of glucagon-like peptide 2 (GLP-2) and of key growth factors on the proliferation of cultured rat astrocytes. Evidence for reciprocal upregulation of the mRNAs for GLP-2 and IGF-I receptors.
The aim of this work was to determine whether the stimulating effect of glucagon-like peptide (GLP)-2 on astrocyte proliferation could be reinforced by proliferating substances, including growth factors such as EGF, platelet-derived growth factor, insulin-like growth factor type I (IGF-I) or a hormone such as insulin. Both DNA synthesis and astrocyte density, as well as the expression of c-Fos, Ki-67, proliferating cell nuclear antigen and glial fibrillary acidic proteins, were found to be higher in the presence of GLP-2 than in its absence. In an attempt to get a better understanding of this process, intracellular cyclic adenosine monophosphate (cAMP) production, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and the expression of GLP-2R and IGF-I receptor (IGF-IR) mRNAs were studied in response to growth factors. Our results indicate that, in the presence of different growth factors, GLP-2 does not increase cAMP production but raises ERK 1/2 phosphorylation. In addition, GLP-2R mRNA expression was increased by IGF-I, whilst mRNA expression of IGF-IR was higher in cells incubated with GLP-2 than in control cells. These results suggest for the first time that GLP-2 and several growth factors show synergistic effects on the proliferation of rat astrocytes, a process in which an enhanced expression of GLP-2R and IGF-IR may be involved, providing additional insights into the physiological role of this novel neuropeptide, specially during astroglial regeneration.
Velázquez
Esther
E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Blázquez
Enrique
E
Ruiz-Albusac
Juan Miguel
JM
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D000067758:Glucagon-Like Peptide-2 Receptor; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D018027:Receptors, Glucagon / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1