Silencing of Tenascin-C Inhibited Inflammation and Apoptosis Via PI3K/Akt/NF-κB Signaling Pathway in Subarachnoid Hemorrhage Cell Model

Tenascin-C (TNC) is upregulated in serum and cerebrospinal fluid after subarachnoid hemorrhage (SAH) and the deficiency of TNC could alleviate neuronal apoptosis and neuroinflammation after SAH. However, the specific mechanism of TNC regulating neuronal apoptosis and neuroinflammation after SAH is not well recognized. The aim of this study was to investigate whether PI3K/Akt/ NF-κB signaling pathway is involved in the regulation of TNC on early brain injury after SAH. Oxygen hemoglobin (OxyHb) was used to induce SAH models in PC12 cells, and classified into control, SAH, LY294002, SAH+TNC-siRNA and SAH+TNC-siRNA+LY groups. Western blotting was applied to examine the protein expression of TNC, Caspase-3, Bax, Bcl-2, PI3K, p-Akt, and p-NF-κB. Reverse transcription quantitative polymerase chain reaction was applied to examine the TNC mRNA expression. Cholecystokinin (CCK)-8 and flow cytometry were used to examine cell proliferation and apoptosis, respectively. ELISA was applied to examine the content of interleukin 6, interleukin 1β, and tumor necrosis factor α. We showed that the TNC protein was highly expressed in SAH cell model. OxyHb inhibited cell proliferation, promoted cell apoptosis and the expression of proapoptotic protein, and promoted proinflammatory cytokine secretion in PC12 cells, which were restored following TNC gene silencing. Moreover, OxyHb decreased the expression of PI3K and p-Akt and increased the expression of p-NF-κB p65 in PC12 cells, which were activated following TNC gene silencing. The LY294002 weakened the effect of TNC gene silencing. The TNC gene silencing relieved neuronal apoptosis and neuroinflammation by activating the PI3K/Akt/ NF-κB signaling pathway. TNC-induced neuroinflammation would be a new target to improve outcome after SAH.