Role of JAK2 in the Proliferation of Activated Astrocytes
After brain injury such as trauma or stroke, astrocytes undergo proliferation and activation which is characterized by increased expression of GFAP. Although reactive astrocytes have some regenerative properties, the astrogliosis is thought to be a barrier to repair in the central nervous system. The activated astrocytes secrete many types of cytokines and inflammatory mediators, which might be associated with JAK2/STAT pathway. Although the inhibition of JAK2 pathway might be able to mitigate the astrogliosis, it is not yet confirmed in vivo study and the role of JAK2 especially on proliferation. In the present study, systemic administration of AG490, a JAK2 inhibitor remarkably reduced the reactive astrogliosis in cortical swab injury. To investigate the role of JAK2 on proliferation of astroglial cells, JAK2 phosphorylation and the effects of JAK2 inhibitors on thrombin-induced astrocyte proliferation were performed. In primary astrocyte cultures obtained from postnatal 1 day mice, the proliferation was induced by thrombin(1U/ml) as mitogenic activator, which can be in-flowed in the brain through the breakdown of the blood-brain barrier during brain injury. The proliferation induced by thrombin was measured with BrdU(+) cells in culture astrocytes. AG490(3-30μM) significantly reduced the astrocyte proliferation in dose-dependent manner and other JAK2 inhibitor, J2I(25μM) also showed like this. In wound-healing model, the proliferation and migration of astrocytes also are reduced by JAK2 inhibition. Taken together, these data show that JAK2 plays an important role in the modulation of astrogliosis and the injury-induced astrogliosis can be prevented by JAK2 inhibitors through modulation of astrocyte proliferation.
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