Transmural compression-induced proliferation and DNA synthesis through activation of a tyrosine kinase pathway in rat astrocytoma RCR-1 cells

Abstract

Gliosis results from abnormal proliferation of glial cells and often occurs in response to brain or spinal cord injury. There are many factors that trigger gliosis associated with such injuries, including ischemia, humoral factors produced by the injured tissue, and possibly mechanical compression itself. In the present study, the effects of mechanical compression on cell proliferation and DNA synthesis were examined in vitro with the rat astrocyte cell line RCR-1. Pressure was applied to cells by instilling compressed helium into sealed plates or flasks in which the partial pressure of oxygen were maintained constant. Compression resulted in time- and intensity-dependent increases in cell number and [3H]thymidine incorporation, with maximum effects apparent at 10 min and 120 mmHg. Compression-induced cell proliferation and DNA synthesis were not inhibited by gadolinium (Gd3+), a blocker of stretch-activated ion channels, or by inhibitors of protein kinase A, protein kinase C, or Ca2+/calmodulin-dependent protein kinases. However, the tyrosine kinase inhibitor genistein inhibited these effects of compression in a concentration-dependent manner. Conditioned medium from compressed cells also induced cell proliferation and DNA synthesis at atmospheric pressure in a genistein-sensitive manner. These results suggest that transmural compression triggers the release of a factor (or factors) that induces cell proliferation and DNA synthesis through a tyrosine kinase pathway in RCR-1 cells.