Fibroblast growth factor 2 mRNA expression evoked by amitriptyline involves extracellular signal‐regulated kinase‐dependent early growth response 1 production in rat primary cultured astrocytes

This study defined the signaling cascade that mediates amitriptyline‐induced FGF2 production in rat primary cultured astrocytes. Amitriptyline treatment significantly increased early growth response 1 (EGR1), a transcription factor known to regulate FGF2 expression. Knockdown of EGR1 using siRNA blocked amitriptyline‐evoked FGF2 mRNA expression. Treatment with several different classes of antidepressants leads to expression of EGR1 mRNA as well as FGF2 mRNA. These results confirm that EGR1 production is likely to be indispensable for the amitriptyline‐evoked FGF2 mRNA expression. Signal transduction inhibitors were used to elaborate the cellular signaling cascade that leads to EGR1‐mediated FGF2 expression following amitriptyline treatment. Amitriptyline‐evoked EGR1‐mediated FGF2 mRNA expression was blocked by mitogen‐activated protein kinase/extracellular signal‐regulated kinase kinase (MEK)1/2 inhibitor. Furthermore, extracellular signal‐regulated kinase/EGR1‐mediated FGF2 mRNA expression evoked by amitriptyline was blocked by inhibitors of the FGF receptor, epidermal growth factor receptor (EGFR), and matrix metalloproteinase. Taken together, these results demonstrate that amitriptyline increases FGF2 mRNA expression through a matrix metalloproteinase/receptor tyrosine kinases (RTK) (FGF receptor and EGFR)/extracellular signal‐regulated kinase/EGR1 signaling pathway in rat primary cultured astrocytes. Recent studies suggest that fibroblast growth fact...
Source: Journal of Neurochemistry - Category: Neurology Authors: Tags: Original Article Source Type: research