Stretch-induced endothelin-1 production by astrocytes

Astrocytes proliferate during central nervous system (CNS) development and then remain quiescent. However, at a site of brain injury, astrocytes re-en ter the cell cycle and undergo complex biochemical/functional changes known as reactive gliosis. Gliosis is the most important histopathologic indicat or of CNS injury, regardless of etiology. Endothelins (ETs) have powerful m itogenic effects on astrocytes and have recently been implicated in the ind uction of gliosis. Reactive astrocytes produce, store, secrete and bind end othelin-1 (ET-1). The stimuli responsible for activating ET production in a strocytes are unresolved. Because of the relationship between stretch and E T production in other cell types, and the observation that ET-1-positive re active astrocytes appear in mechanically deformed regions, we are examining whether mechanical deformation affects ET-1 production. We expose mature r at astrocyte cultures to mechanical stress using flexible-bottomed culture plates, Mechanical stretch of quiescent, confluent cultures causes an incre ase in cytoplasmic Ca2+ and inositol trisphosphate (IP3), and a substantial increase in ET-1 production and secretion into the culture media.