The Role of Integrin αvβ8 in Neonatal Hypoxic-Ischemic Brain Injury

Integrin alpha(v)beta 8 plays an important role in cerebral vascular development. It has been proven that av beta(8) is a key factor for transforming growth factor-beta 1 (TGF-beta 1) activation in epithelial cells. However, it is not clear whether alpha(v)beta(8) can activate TGF-beta 1 and play a role in protection during neonatal hypoxic-ischemic brain injury. In this study, we investigated the relationship between alpha(v)beta(8) and TGF-beta 1 activation, and thus the effects of TGF-beta 1 activation in the protection of neurons after hypoxiaischemia (HI). Astrocytes and neurons from rat brains were cultured and then subjected to oxygen-glucose deprivation to generate HI model in vitro. beta(8) expression was determined using immunocytochemistry, western blot, and reverse-transcriptase polymerase chain reaction. TGF-beta 1 activation was determined by TGF-beta bioassay in a tested cell (astrocyte) and a reporter cell co-culture system. The pro-apoptotic protein, cleaved caspase-3, and the antiapoptotic protein, Bcl-2 and Bcl-xL, were detected using western blot. Cellular apoptosis was detected with TUNEL. We found that beta(8) expression was stronger in astrocytes than that in neurons under normoxia. HI resulted in a rapid and persistent increase of beta(8) expression in astrocytes, but only in a slight and transient increase in neurons. Astrocytes beta(8) could induce TGF-beta 1 leading to upregulation of Bcl-2 and Bcl-xL, and thus attenuated neuronal apoptosis. The present findings suggest that beta(8) protecting the brain against neonatal HI injury through TGF-beta 1 signaling pathway, which may have implications for the treatment of HI brain injury.